S-Adenosylmethionine Treatment Diminishes the Proliferation of Castration-Resistant Prostate Cancer Cells by Modulating the Expression of miRNAs

Thomas Schmidt

doi:10.2478/aite-2024-0022

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S-Adenosylmethionine Treatment Diminishes the Proliferation of Castration-Resistant Prostate Cancer Cells by Modulating the Expression of miRNAs

Archivum Immunologiae et Therapiae Experimentalis

Volume 72 (2024): Issue 1 (January 2024)

By: Thomas Schmidt

Open Access

|Nov 2024

Figures & Tables

Detection of differentially expressed miRNAs in PC-3 cells treated with SAM and controls. **(A)** Heatmap of differentially expressed miRNAs in PC-3 cells treated with SAM and untreated controls. Seventeen differentially expressed mature miRNAs (7 upregulated and 10 downregulated) were detected (P < 0.005). Clustering clearly distinguished between the treated samples and controls as well as between the upregulated and downregulated groups. **(B)** A volcano plot displaying the differentially expressed miRNAs. miRNAs, microRNA; SAM, S-adenosylmethionine.

Combined analyses of miRNA expression and RNA-seq data. The differentially expressed genes of the transcriptome that were matched to target genes were detected via three different miRNA databases (miRDB, TargetScan, and miRanda). **(A)** A total of 92 downregulated genes were associated with upregulated miRNAs, and **(B)** 41 upregulated genes were associated with downregulated miRNAs. The genes are shown in the boxes. **(C)** Gene expression levels of StarD13 following treatment with 200 μm SAM. A significant increase in the expression of StarD13 was observed (211% of the control). miRNA, microRNA; SAM, S-adenosylmethionine; StarD13, StAR-related lipid transfer domain containing 13.

(A) Differential expression of hsa-miR-192-5p (after 24, 48, and 120 h) in untreated PC-3 cells or mock-transfected PC-3 cells. Since both groups displayed almost no differences, we described them as controls and set them to 100%. The expression of hsa-miR-192-5p was significantly downregulated following treatment with SAM (60% of the control after 48 h and 45% after 120 h), after transfection with the miRNA agomir (70% of the control after 24 h, 29% of the control after 48 h, and 19% after 120 h), or after combination treatment (68% of the control after 24 h, 13% of the control after 48 h, and 9% of the control after 120 h). **(B)** Transfection with the hsa-miR-192-5p agomir alone or in combination with SAM inhibited the proliferation of PC-3 cells. Twenty-four hours after PC-3 cells were transfected with the hsa-miR-192-5p agomir, and the cells were seeded in 96-well plates and grown for 24 h, 48 h, or 120 h. Proliferation was measured using the 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium bromide assay. Differences between untransfected PC-3 cells (PC-3) and mock-transfected PC-3 cells (miR-NC) were hardly detectable. Transfection with the hsa-miR-192-5p agomir resulted in significantly diminished proliferation of 71% (after 48 h) and 62% (after 120 h) compared to that of the controls. A combination of SAM treatment and transfection with the miRNA agomir decreased the proliferation rate of PC-3 cells even more clearly (70% of the control after 24 h, 40% of the control after 48 h, and 23% of the control after 120 h). **(C)** A fluorogenic caspase activity assay revealed a significant upregulation of the caspase-3 activity in PC-3 cells after transfection with hsa-miR-192-5p agomir or a combination of SAM treatment and hsa-miR-192-5p agomir transfection for 120 h. The results are expressed as the means ± SDs of three independent experiments: ^*P < 0.01, ^**P < 0.001, ^***P < 0.0001, and ^****P < 0.00001. miRNA, microRNA; SAM, S-adenosylmethionine.

GO term enrichment and KEGG pathway analysis of differentially methylated regions. Differentially expressed transcripts identified in **(A)** downregulated expression genes and in **(B)** upregulated expression genes. GO enrichment was used to identify enriched regulatory motifs, molecular functions, BP, and CC, as was KEGG pathway enrichment **(C)**. BP, biological process; CC, cellular component; GO, gene ontology.

Table S1.

Functional enrichment analysis (BP) of the downregulated genes

ID	Description	GeneRatio	BgRatio	p value	p.adjust	q-value	geneID	Count
GO:0048485	Sympathetic nervous system development	4/86	21/18866	2.27016E-06	0.002377266	0.001927173	GATA3/SOX4/SEMA3A/TP63	4
GO:0003283	Atrial septum development	4/86	23/18866	3.3355E-06	0.002377266	0.001927173	TGFB2/SOX4/ANK2/BMPR2	4
GO:0003179	Heart valve morphogenesis	5/86	52/18866	3.8427E-06	0.002377266	0.001927173	GATA3/SMAD6/TGFB2/SOX4/BMPR2	5
GO:0003181	Atrioventricular valve morphogenesis	4/86	24/18866	3.9887E-06	0.002377266	0.001927173	SMAD6/TGFB2/SOX4/BMPR2	4
GO:0003171	Atrioventricular valve development	4/86	26/18866	5.57292E-06	0.002481207	0.002011434	SMAD6/TGFB2/SOX4/BMPR2	4
GO:0031069	Hair follicle morphogenesis	4/86	28/18866	7.57961E-06	0.002481207	0.002011434	FST/TGFB2/ATP7A/TP63	4
GO:0003170	Heart valve development	5/86	61/18866	8.51768E-06	0.002481207	0.002011434	GATA3/SMAD6/TGFB2/SOX4/BMPR2	5
GO:0003183	Mitral valve morphogenesis	3/86	10/18866	1.07242E-05	0.002481207	0.002011434	SMAD6/SOX4/BMPR2	3
GO:0071772	Response to BMP	7/86	168/18866	1.16587E-05	0.002481207	0.002011434	SORL1/FST/GATA3/SKIL/SMAD6/TGFB2/BMPR2	7
GO:0071773	Cellular response to BMP stimulus	7/86	168/18866	1.16587E-05	0.002481207	0.002011434	SORL1/FST/GATA3/SKIL/SMAD6/TGFB2/BMPR2	7
GO:0048880	Sensory system development	10/86	394/18866	1.2143E-05	0.002481207	0.002011434	SLC7A11/COL8A1/GATA3/CLIC4/SKIL/TGFB2/BDNF/SEMA3A/SLITRK6/BMPR2	10
GO:0048730	Epidermis morphogenesis	4/86	32/18866	1.31282E-05	0.002481207	0.002011434	FST/TGFB2/ATP7A/TP63	4
GO:0003279	Cardiac septum development	6/86	114/18866	1.35301E-05	0.002481207	0.002011434	GATA3/SMAD6/TGFB2/SOX4/ANK2/BMPR2	6
GO:0003174	Mitral valve development	3/86	11/18866	1.46971E-05	0.002502712	0.002028868	SMAD6/SOX4/BMPR2	3
GO:0003230	Cardiac atrium development	4/86	36/18866	2.12083E-05	0.003370699	0.002732516	TGFB2/SOX4/ANK2/BMPR2	4
GO:1905314	Semi-lunar valve development	4/86	37/18866	2.36965E-05	0.003515909	0.002850233	GATA3/SMAD6/TGFB2/BMPR2	4
GO:0003281	Ventricular septum development	5/86	76/18866	2.50715E-05	0.003515909	0.002850233	GATA3/SMAD6/TGFB2/SOX4/BMPR2	5
GO:0060413	Atrial septum morphogenesis	3/86	16/18866	4.9065E-05	0.006498385	0.00526803	TGFB2/SOX4/BMPR2	3
GO:0048483	Autonomic nervous system development	4/86	47/18866	6.18134E-05	0.007400207	0.005999108	GATA3/SOX4/SEMA3A/TP63	4
GO:0001654	Eye development	9/86	384/18866	6.30723E-05	0.007400207	0.005999108	SLC7A11/COL8A1/GATA3/CLIC4/SKIL/TGFB2/BDNF/SLITRK6/BMPR2	9
GO:0030510	Regulation of BMP signaling pathway	5/86	93/18866	6.63775E-05	0.007400207	0.005999108	SORL1/FST/SKIL/SMAD6/BMPR2	5
GO:0150063	Visual system development	9/86	388/18866	6.82905E-05	0.007400207	0.005999108	SLC7A11/COL8A1/GATA3/CLIC4/SKIL/TGFB2/BDNF/SLITRK6/BMPR2	9
GO:0030509	BMP signaling pathway	6/86	155/18866	7.63551E-05	0.007914368	0.006415922	SORL1/FST/SKIL/SMAD6/TGFB2/BMPR2	6
GO:0003215	Cardiac right ventricle morphogenesis	3/86	20/18866	9.85737E-05	0.009791656	0.007937778	GATA3/TGFB2/SOX4	3
GO:0003177	Pulmonary valve development	3/86	21/18866	0.000114624	0.010930574	0.008861062	SMAD6/TGFB2/BMPR2	3
GO:0016358	Dendrite development	7/86	247/18866	0.000135064	0.012023407	0.009746987	CPEB3/PPP1R9A/BDNF/SEMA3A/PRKG1/PACSIN1/MAP2	7
GO:0043010	Camera-type eye development	8/86	332/18866	0.000136171	0.012023407	0.009746987	SLC7A11/COL8A1/GATA3/CLIC4/SKIL/TGFB2/SLITRK6/BMPR2	8
GO:0003205	Cardiac chamber development	6/86	174/18866	0.000144194	0.012277131	0.009952673	GATA3/SMAD6/TGFB2/SOX4/ANK2/BMPR2	6
GO:0010634	Positive regulation of epithelial cell migration	6/86	176/18866	0.000153468	0.01261616	0.010227512	GATA3/SASH1/TGFB2/HDAC9/BMPR2/ITGB3	6
GO:0090092	Regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	7/86	254/18866	0.000160478	0.012752643	0.010338155	SORL1/FST/SKIL/SMAD6/TGFB2/INHBB/BMPR2	7
GO:0060393	Regulation of pathway-restricted SMAD protein phosphorylation	4/86	62/18866	0.000183531	0.014114136	0.011441873	SMAD6/TGFB2/INHBB/BMPR2	4
GO:0060037	Pharyngeal system development	3/86	26/18866	0.000220418	0.015457062	0.012530539	GATA3/TGFB2/BMPR2	3
GO:0060384	Innervation	3/86	26/18866	0.000220418	0.015457062	0.012530539	GABRB3/SEMA3A/SLITRK6	3
GO:0060389	Pathway-restricted SMAD protein phosphorylation	4/86	65/18866	0.000220445	0.015457062	0.012530539	SMAD6/TGFB2/INHBB/BMPR2	4
GO:0003148	Outflow tract septum morphogenesis	3/86	27/18866	0.000247155	0.016834784	0.013647414	SMAD6/TGFB2/BMPR2	3
GO:0031032	Actomyosin structure organization	6/86	200/18866	0.000306151	0.020274023	0.016435493	PPP1R9A/NEBL/CGNL1/PGM5/ARHGAP28/MYO18A	6
GO:0003206	Cardiac chamber morphogenesis	5/86	131/18866	0.000331986	0.020492366	0.016612497	GATA3/SMAD6/TGFB2/SOX4/BMPR2	5
GO:0003231	Cardiac ventricle development	5/86	131/18866	0.000331986	0.020492366	0.016612497	GATA3/SMAD6/TGFB2/SOX4/BMPR2	5
GO:0003209	Cardiac atrium morphogenesis	3/86	30/18866	0.00033969	0.020492366	0.016612497	TGFB2/SOX4/BMPR2	3
GO:0010595	Positive regulation of endothelial cell migration	5/86	132/18866	0.000343832	0.020492366	0.016612497	GATA3/SASH1/HDAC9/BMPR2/ITGB3	5
GO:0032535	Regulation of cellular component size	8/86	383/18866	0.000358164	0.020825902	0.016882884	PPP1R9A/BDNF/SEMA3A/ATP7A/ARHGAP28/BMPR2/JMY/MAP2	8
GO:0051497	Negative regulation of stress fiber assembly	3/86	31/18866	0.00037485	0.021277191	0.017248729	PPP1R9A/CGNL1/ARHGAP28	3
GO:0003176	Aortic valve development	3/86	32/18866	0.000412269	0.022856978	0.018529411	GATA3/SMAD6/BMPR2	3
GO:0060411	Cardiac septum morphogenesis	4/86	77/18866	0.00042271	0.022903202	0.018566884	SMAD6/TGFB2/SOX4/BMPR2	4
GO:0010632	Regulation of epithelial cell migration	7/86	301/18866	0.000449424	0.023809483	0.019301576	GATA3/SASH1/TGFB2/SEMA3A/HDAC9/BMPR2/ITGB3	7
GO:0021675	Nerve development	4/86	79/18866	0.000466089	0.024155573	0.01958214	GABRB3/BDNF/SEMA3A/SLITRK6	4
GO:0032232	Negative regulation of actin filament bundle assembly	3/86	34/18866	0.000494123	0.025063604	0.020318252	PPP1R9A/CGNL1/ARHGAP28	3
GO:0010769	Regulation of cell morphogenesis involved in differentiation	7/86	310/18866	0.000535603	0.025683957	0.020821152	PPP1R9A/SKIL/BDNF/SEMA3A/BMPR2/MAP2/NEDD9	7
GO:0090287	Regulation of cellular response to growth factor stimulus	7/86	310/18866	0.000535603	0.025683957	0.020821152	SORL1/FST/GATA3/SKIL/SMAD6/BMPR2/ITGB3	7
GO:0110111	Negative regulation of animal organ morphogenesis	3/86	35/18866	0.000538674	0.025683957	0.020821152	GATA3/TGFB2/BMPR2	3
GO:0002088	Lens development in camera-type eye	4/86	83/18866	0.000562221	0.026281074	0.021305215	SLC7A11/GATA3/SKIL/SLITRK6	4
GO:0000289	Nuclear-transcribed mRNA poly(A) tail shortening	3/86	36/18866	0.000585716	0.026852821	0.021768712	CPEB3/TNRC6C/CNOT6L	3
GO:0016331	Morphogenesis of embryonic epithelium	5/86	151/18866	0.000635718	0.028595307	0.023181289	GATA3/TGFB2/SOX4/MTHFR/TP63	5
GO:0001942	Hair follicle development	4/86	87/18866	0.00067167	0.029652983	0.024038713	FST/TGFB2/ATP7A/TP63	4
GO:0007050	Cell cycle arrest	6/86	234/18866	0.000702266	0.030276819	0.024544437	SKIL/TGFB2/SOX4/JMY/TP53INP1/CNOT6L	6
GO:0022404	Molting cycle process	4/86	89/18866	0.000731697	0.030276819	0.024544437	FST/TGFB2/ATP7A/TP63	4
GO:0022405	Hair cycle process	4/86	89/18866	0.000731697	0.030276819	0.024544437	FST/TGFB2/ATP7A/TP63	4
GO:1902904	Negative regulation of supramolecular fiber organization	5/86	156/18866	0.0007366	0.030276819	0.024544437	PPP1R9A/CGNL1/TTBK2/ARHGAP28/MAP2	5
GO:0098773	Skin epidermis development	4/86	90/18866	0.000763091	0.030834037	0.024996155	FST/TGFB2/ATP7A/TP63	4
GO:1902895	Positive regulation of pri-miRNA transcription by RNA polymerase II	3/86	40/18866	0.000799907	0.031782969	0.025765423	GATA3/SMAD6/TGFB2	3
GO:0048286	Lung alveolus development	3/86	41/18866	0.000860228	0.03260155	0.026429021	SLC7A11/ATP7A/BMPR2	3
GO:0014909	Smooth muscle cell migration	4/86	93/18866	0.000862978	0.03260155	0.026429021	SORL1/ATP7A/PRKG1/ITGB3	4
GO:0009267	Cellular response to starvation	5/86	163/18866	0.000897377	0.03260155	0.026429021	NUAK1/SLC38A2/GABARAPL1/INHBB/BMPR2	5
GO:0051494	Negative regulation of cytoskeleton organization	5/86	163/18866	0.000897377	0.03260155	0.026429021	PPP1R9A/CGNL1/TTBK2/ARHGAP28/MAP2	5
GO:0045713	Low-density lipoprotein particle receptor biosynthetic process	2/86	10/18866	0.00090256	0.03260155	0.026429021	ITGAV/ITGB3	2
GO:1904526	Regulation of microtubule binding	2/86	10/18866	0.00090256	0.03260155	0.026429021	TTBK2/MAP2	2
GO:0051100	Negative regulation of binding	5/86	169/18866	0.001054847	0.037420693	0.030335744	SORL1/RSF1/TTBK2/ARHGAP28/MAP2	5
GO:0050673	Epithelial cell proliferation	8/86	453/18866	0.001072913	0.037420693	0.030335744	FST/COL8A1/GATA3/TGFB2/ATP7A/BMPR2/ITGB3/TP63	8
GO:0098917	Retrograde transsynaptic signaling	2/86	11/18866	0.001099862	0.037420693	0.030335744	BDNF/PLCB1	2
GO:0032924	Activin receptor signaling pathway	3/86	45/18866	0.001130155	0.037420693	0.030335744	FST/INHBB/BMPR2	3
GO:0046189	Phenol-containing compound biosynthetic process	3/86	45/18866	0.001130155	0.037420693	0.030335744	SLC7A11/GATA3/TGFB2	3
GO:0060412	Ventricular septum morphogenesis	3/86	45/18866	0.001130155	0.037420693	0.030335744	TGFB2/SOX4/BMPR2	3
GO:0060840	Artery development	4/86	102/18866	0.001217645	0.038883859	0.031521885	SMAD6/TGFB2/SOX4/BMPR2	4
GO:0007178	Transmembrane receptor protein serine/threonine kinase signaling pathway	7/86	359/18866	0.001263006	0.038883859	0.031521885	SORL1/FST/SKIL/SMAD6/TGFB2/INHBB/BMPR2	7
GO:0050919	Negative chemotaxis	3/86	47/18866	0.001282991	0.038883859	0.031521885	SEMA3A/ITGAV/ITGB3	3
GO:0070997	Neuron death	7/86	360/18866	0.001283364	0.038883859	0.031521885	SORL1/SLC7A11/GATA3/GABRB3/TGFB2/BDNF/TP63	7
GO:0051798	Positive regulation of hair follicle development	2/86	12/18866	0.001315929	0.038883859	0.031521885	FST/TGFB2	2
GO:0060213	Positive regulation of nuclear-transcribed mRNA poly(A) tail shortening	2/86	12/18866	0.001315929	0.038883859	0.031521885	CPEB3/TNRC6C	2
GO:0010862	Positive regulation of pathway-restricted SMAD protein phosphorylation	3/86	48/18866	0.001364044	0.038883859	0.031521885	TGFB2/INHBB/BMPR2	3
GO:0072331	Signal transduction by p53 class mediator	6/86	267/18866	0.001386923	0.038883859	0.031521885	NUAK1/SOX4/JMY/TP53INP1/TP63/CNOT6L	6
GO:0010631	Epithelial cell migration	7/86	365/18866	0.001389051	0.038883859	0.031521885	GATA3/SASH1/TGFB2/SEMA3A/HDAC9/BMPR2/ITGB3	7
GO:0014812	Muscle cell migration	4/86	106/18866	0.001403922	0.038883859	0.031521885	SORL1/ATP7A/PRKG1/ITGB3	4
GO:0008361	Regulation of cell size	5/86	181/18866	0.001430229	0.038883859	0.031521885	BDNF/SEMA3A/ATP7A/BMPR2/MAP2	5
GO:0048736	Appendage development	5/86	181/18866	0.001430229	0.038883859	0.031521885	SLC7A11/TGFB2/SOX4/BMPR2/TP63	5
GO:0060173	Limb development	5/86	181/18866	0.001430229	0.038883859	0.031521885	SLC7A11/TGFB2/SOX4/BMPR2/TP63	5
GO:0051098	Regulation of binding	7/86	367/18866	0.001433187	0.038883859	0.031521885	SORL1/GATA3/RSF1/BDNF/TTBK2/ARHGAP28/MAP2	7
GO:0090132	Epithelium migration	7/86	368/18866	0.001455662	0.038883859	0.031521885	GATA3/SASH1/TGFB2/SEMA3A/HDAC9/BMPR2/ITGB3	7
GO:0061014	Positive regulation of mRNA catabolic process	3/86	50/18866	0.001535648	0.038883859	0.031521885	CPEB3/TNRC6C/CNOT6L	3
GO:0010745	Negative regulation of macrophage derived foam cell differentiation	2/86	13/18866	0.001550587	0.038883859	0.031521885	ITGAV/ITGB3	2
GO:0042415	Norepinephrine metabolic process	2/86	13/18866	0.001550587	0.038883859	0.031521885	GATA3/ATP7A	2
GO:0042635	Positive regulation of hair cycle	2/86	13/18866	0.001550587	0.038883859	0.031521885	FST/TGFB2	2
GO:1903651	Positive regulation of cytoplasmic transport	2/86	13/18866	0.001550587	0.038883859	0.031521885	SORL1/MAP2	2
GO:0018958	Phenol-containing compound metabolic process	4/86	109/18866	0.001556068	0.038883859	0.031521885	SLC7A11/GATA3/TGFB2/ATP7A	4
GO:0007409	Axonogenesis	8/86	482/18866	0.001590594	0.038883859	0.031521885	GATA3/SKIL/ETV1/BDNF/SEMA3A/SLITRK6/BMPR2/MAP2	8
GO:0090130	Tissue migration	7/86	374/18866	0.00159637	0.038883859	0.031521885	GATA3/SASH1/TGFB2/SEMA3A/HDAC9/BMPR2/ITGB3	7
GO:0051051	Negative regulation of transport	8/86	483/18866	0.001611458	0.038883859	0.031521885	PPP1R9A/SESTD1/ATP7A/HDAC9/ITGAV/INHBB/PACSIN1/ITGB3	8
GO:0050770	Regulation of axonogenesis	5/86	186/18866	0.001612647	0.038883859	0.031521885	SKIL/BDNF/SEMA3A/BMPR2/MAP2	5
GO:0090102	Cochlea development	3/86	51/18866	0.001626288	0.038883859	0.031521885	GATA3/GABRB3/SLITRK6	3
GO:1902893	Regulation of pri-miRNA transcription by RNA polymerase II	3/86	51/18866	0.001626288	0.038883859	0.031521885	GATA3/SMAD6/TGFB2	3
GO:0042303	Molting cycle	4/86	111/18866	0.001663655	0.038883859	0.031521885	FST/TGFB2/ATP7A/TP63	4
GO:0042633	Hair cycle	4/86	111/18866	0.001663655	0.038883859	0.031521885	FST/TGFB2/ATP7A/TP63	4
GO:0061387	Regulation of extent of cell growth	4/86	111/18866	0.001663655	0.038883859	0.031521885	BDNF/SEMA3A/BMPR2/MAP2	4
GO:0030514	Negative regulation of BMP signaling pathway	3/86	52/18866	0.001720211	0.039815365	0.032277027	SORL1/SKIL/SMAD6	3
GO:0007548	Sex differentiation	6/86	280/18866	0.001764948	0.040458044	0.032798026	FST/GATA3/TGFB2/SEMA3A/INHBB/TP63	6
GO:0060211	Regulation of nuclear-transcribed mRNA poly(A) tail shortening	2/86	14/18866	0.001803668	0.040875705	0.03313661	CPEB3/TNRC6C	2
GO:0061614	Pri-miRNA transcription by RNA polymerase II	3/86	53/18866	0.00181746	0.040875705	0.03313661	GATA3/SMAD6/TGFB2	3
GO:0006584	Catecholamine metabolic process	3/86	54/18866	0.001918077	0.042339775	0.034323484	GATA3/TGFB2/ATP7A	3
GO:0009712	Catechol-containing compound metabolic process	3/86	54/18866	0.001918077	0.042339775	0.034323484	GATA3/TGFB2/ATP7A	3
GO:0030900	Forebrain development	7/86	391/18866	0.002053275	0.044167892	0.03580548	SLC7A11/BCAN/SEMA3A/ATP7A/SLC38A2/PLCB1/PRKG1	7
GO:0048839	Inner ear development	5/86	197/18866	0.002073551	0.044167892	0.03580548	GATA3/GABRB3/TGFB2/BDNF/SLITRK6	5
GO:0007638	Mechanosensory behavior	2/86	15/18866	0.002075002	0.044167892	0.03580548	ETV1/SLITRK6	2
GO:0050746	Regulation of lipoprotein metabolic process	2/86	15/18866	0.002075002	0.044167892	0.03580548	ITGAV/ITGB3	2
GO:0010976	Positive regulation of neuron projection development	6/86	290/18866	0.002105428	0.044418936	0.036008992	CPEB3/PPP1R9A/SKIL/BDNF/BMPR2/PACSIN1	6
GO:0031346	Positive regulation of cell projection organization	7/86	394/18866	0.002143474	0.044824937	0.036338124	CPEB3/PPP1R9A/SKIL/BDNF/ATP7A/BMPR2/PACSIN1	7
GO:0007613	Memory	4/86	121/18866	0.002280062	0.047266679	0.038317566	CPEB3/ATXN1/BDNF/PLCB1	4
GO:0042035	Regulation of cytokine biosynthetic process	2/86	16/18866	0.002364421	0.048592932	0.039392716	GATA3/INHBB	2
GO:0048675	Axon extension	4/86	123/18866	0.00241989	0.049307834	0.039972264	BDNF/SEMA3A/BMPR2/MAP2	4
GO:0042594	Response to starvation	5/86	206/18866	0.002516912	0.050850145	0.041222566	NUAK1/SLC38A2/GABARAPL1/INHBB/BMPR2	5
GO:0001838	Embryonic epithelial tube formation	4/86	125/18866	0.002565513	0.051396495	0.041665474	GATA3/TGFB2/SOX4/MTHFR	4
GO:0035904	Aorta development	3/86	60/18866	0.002594751	0.051549046	0.041789142	SMAD6/TGFB2/SOX4	3
GO:0003184	Pulmonary valve morphogenesis	2/86	17/18866	0.00267176	0.051784349	0.041979895	SMAD6/TGFB2	2
GO:0006750	Glutathione biosynthetic process	2/86	17/18866	0.00267176	0.051784349	0.041979895	SLC7A11/CHAC1	2
GO:1900363	Regulation of mRNA polyadenylation	2/86	17/18866	0.00267176	0.051784349	0.041979895	CPEB3/CCNT1	2
GO:0001704	Formation of primary germ layer	4/86	127/18866	0.002717051	0.052237505	0.042347253	COL8A1/ITGAV/BMPR2/ITGB3	4
GO:0070527	Platelet aggregation	3/86	62/18866	0.002849026	0.054336625	0.044048942	SLC7A11/PRKG1/ITGB3	3
GO:0060080	Inhibitory postsynaptic potential	2/86	18/18866	0.002996851	0.055816359	0.045248514	GABRB3/BDNF	2
GO:0061298	Retina vasculature development in camera-type eye	2/86	18/18866	0.002996851	0.055816359	0.045248514	CLIC4/BMPR2	2
GO:1900153	Positive regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay	2/86	18/18866	0.002996851	0.055816359	0.045248514	CPEB3/TNRC6C	2
GO:0072175	Epithelial tube formation	4/86	133/18866	0.003208333	0.058835885	0.047696346	GATA3/TGFB2/SOX4/MTHFR	4
GO:0090101	Negative regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	4/86	133/18866	0.003208333	0.058835885	0.047696346	SORL1/FST/SKIL/SMAD6	4
GO:0019184	Nonribosomal peptide biosynthetic process	2/86	19/18866	0.003339532	0.060550663	0.049086461	SLC7A11/CHAC1	2
GO:0045785	Positive regulation of cell adhesion	7/86	428/18866	0.003395248	0.060550663	0.049086461	MAGI1/COL8A1/GATA3/TGFB2/SOX4/ITGAV/NEDD9	7
GO:0042490	Mechanoreceptor differentiation	3/86	66/18866	0.00340238	0.060550663	0.049086461	GABRB3/BDNF/SLITRK6	3
GO:0031669	Cellular response to nutrient levels	5/86	221/18866	0.003403435	0.060550663	0.049086461	NUAK1/SLC38A2/GABARAPL1/INHBB/BMPR2	5
GO:1901214	Regulation of neuron death	6/86	321/18866	0.003481234	0.061476012	0.049836611	SORL1/SLC7A11/GATA3/GABRB3/TGFB2/BDNF	6
GO:0008406	Gonad development	5/86	223/18866	0.00353664	0.06199522	0.050257517	FST/GATA3/TGFB2/SEMA3A/INHBB	5
GO:0043583	Ear development	5/86	224/18866	0.003604631	0.062552759	0.050709496	GATA3/GABRB3/TGFB2/BDNF/SLITRK6	5
GO:0007015	Actin filament organization	7/86	434/18866	0.003664496	0.062552759	0.050709496	PPP1R9A/NEBL/CGNL1/ARHGAP28/PACSIN1/JMY/NEDD9	7
GO:0002320	Lymphoid progenitor cell differentiation	2/86	20/18866	0.003699639	0.062552759	0.050709496	GATA3/SOX4	2
GO:0042089	Cytokine biosynthetic process	2/86	20/18866	0.003699639	0.062552759	0.050709496	GATA3/INHBB	2
GO:1900151	Regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay	2/86	20/18866	0.003699639	0.062552759	0.050709496	CPEB3/TNRC6C	2
GO:0045137	Development of primary sexual characteristics	5/86	229/18866	0.003958763	0.065577145	0.053161267	FST/GATA3/TGFB2/SEMA3A/INHBB	5
GO:0001655	Urogenital system development	6/86	330/18866	0.003983793	0.065577145	0.053161267	GATA3/SMAD6/TGFB2/SOX4/BDNF/TP63	6
GO:0009713	Catechol-containing compound biosynthetic process	2/86	21/18866	0.004077009	0.065577145	0.053161267	GATA3/TGFB2	2
GO:0042107	Cytokine metabolic process	2/86	21/18866	0.004077009	0.065577145	0.053161267	GATA3/INHBB	2
GO:0042423	Catecholamine biosynthetic process	2/86	21/18866	0.004077009	0.065577145	0.053161267	GATA3/TGFB2	2
GO:0051797	Regulation of hair follicle development	2/86	21/18866	0.004077009	0.065577145	0.053161267	FST/TGFB2	2
GO:0060065	Uterus development	2/86	21/18866	0.004077009	0.065577145	0.053161267	GATA3/TGFB2	2
GO:0048608	Reproductive structure development	7/86	443/18866	0.004098572	0.065577145	0.053161267	FST/GATA3/TGFB2/SEMA3A/INHBB/BMPR2/TP63	7
GO:0015800	Acidic amino acid transport	3/86	71/18866	0.004180801	0.066006816	0.053509587	SLC7A11/BDNF/SLC38A2	3
GO:0033627	Cell adhesion mediated by integrin	3/86	71/18866	0.004180801	0.066006816	0.053509587	TGFB2/ITGAV/ITGB3	3
GO:0061458	Reproductive system development	7/86	447/18866	0.004303588	0.06749838	0.05471875	FST/GATA3/TGFB2/SEMA3A/INHBB/BMPR2/TP63	7
GO:0070988	Demethylation	3/86	72/18866	0.004348359	0.067754826	0.054926642	GATA3/TET2/JMJD1C	3
GO:0043254	Regulation of protein-containing complex assembly	7/86	449/18866	0.004408972	0.068253172	0.055330636	SORL1/PPP1R9A/SMAD6/ARHGAP28/ATF7IP/JMY/MAP2	7
GO:0010888	Negative regulation of lipid storage	2/86	22/18866	0.004471481	0.068774263	0.055753068	ITGAV/ITGB3	2
GO:0003208	Cardiac ventricle morphogenesis	3/86	73/18866	0.004519944	0.069074013	0.055996065	GATA3/TGFB2/SOX4	3
GO:0051047	Positive regulation of secretion	6/86	340/18866	0.00460332	0.069900087	0.056665737	SORL1/SYTL2/TGFB2/SOX4/MYO18A/INHBB	6
GO:0010594	Regulation of endothelial cell migration	5/86	238/18866	0.004657999	0.070185555	0.056897156	GATA3/SASH1/HDAC9/BMPR2/ITGB3	5
GO:0050804	Modulation of chemical synaptic transmission	7/86	454/18866	0.004681	0.070185555	0.056897156	CPEB3/PPP1R9A/FBXL20/SLC7A11/SLC24A1/BDNF/PLCB1	7
GO:0099177	Regulation of trans-synaptic signaling	7/86	455/18866	0.004736897	0.070579766	0.05721673	CPEB3/PPP1R9A/FBXL20/SLC7A11/SLC24A1/BDNF/PLCB1	7
GO:0048844	Artery morphogenesis	3/86	75/18866	0.004875303	0.070980628	0.057541696	TGFB2/SOX4/BMPR2	3
GO:0050805	Negative regulation of synaptic transmission	3/86	75/18866	0.004875303	0.070980628	0.057541696	PPP1R9A/SLC24A1/BDNF	3
GO:1900006	Positive regulation of dendrite development	3/86	75/18866	0.004875303	0.070980628	0.057541696	CPEB3/PPP1R9A/PACSIN1	3
GO:0032799	Low-density lipoprotein receptor particle metabolic process	2/86	23/18866	0.004882896	0.070980628	0.057541696	ITGAV/ITGB3	2
GO:0035148	Tube formation	4/86	150/18866	0.004922269	0.071119327	0.057654135	GATA3/TGFB2/SOX4/MTHFR	4
GO:0051402	Neuron apoptotic process	5/86	245/18866	0.005259584	0.075535237	0.06123397	GATA3/GABRB3/TGFB2/BDNF/TP63	5
GO:0010869	Regulation of receptor biosynthetic process	2/86	24/18866	0.005311093	0.075818242	0.061463393	ITGAV/ITGB3	2
GO:0050708	Regulation of protein secretion	6/86	352/18866	0.005437537	0.076277029	0.061835316	SORL1/TGFB2/SOX4/HDAC9/MYO18A/INHBB	6
GO:0000288	Nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay	3/86	78/18866	0.005439218	0.076277029	0.061835316	CPEB3/TNRC6C/CNOT6L	3
GO:0060395	SMAD protein signal transduction	3/86	78/18866	0.005439218	0.076277029	0.061835316	SMAD6/TGFB2/INHBB	3
GO:0009636	Response to toxic substance	5/86	250/18866	0.005721706	0.079503569	0.064450968	PPP1R9A/AHR/SLC7A11/ATP7A/TP53INP1	5
GO:0010770	Positive regulation of cell morphogenesis involved in differentiation	4/86	157/18866	0.00577791	0.079503569	0.064450968	SKIL/BDNF/BMPR2/NEDD9	4
GO:0051017	Actin filament bundle assembly	4/86	157/18866	0.00577791	0.079503569	0.064450968	PPP1R9A/CGNL1/ARHGAP28/NEDD9	4
GO:0031667	Response to nutrient levels	7/86	473/18866	0.005832	0.079503569	0.064450968	SORL1/NUAK1/MTHFR/SLC38A2/GABARAPL1/INHBB/BMPR2	7
GO:0003151	Outflow tract morphogenesis	3/86	80/18866	0.005836042	0.079503569	0.064450968	SMAD6/TGFB2/BMPR2	3
GO:0031668	Cellular response to extracellular stimulus	5/86	253/18866	0.006012367	0.081440239	0.066020964	NUAK1/SLC38A2/GABARAPL1/INHBB/BMPR2	5
GO:0021884	Forebrain neuron development	2/86	26/18866	0.006217208	0.082775094	0.067103088	SEMA3A/ATP7A	2
GO:1903649	Regulation of cytoplasmic transport	2/86	26/18866	0.006217208	0.082775094	0.067103088	SORL1/MAP2	2
GO:0021954	Central nervous system neuron development	3/86	82/18866	0.006249797	0.082775094	0.067103088	SEMA3A/ATP7A/MAP2	3
GO:1903313	Positive regulation of mRNA metabolic process	3/86	82/18866	0.006249797	0.082775094	0.067103088	CPEB3/TNRC6C/CNOT6L	3
GO:0061572	Actin filament bundle organization	4/86	161/18866	0.006308804	0.08305588	0.067330711	PPP1R9A/CGNL1/ARHGAP28/NEDD9	4
GO:0001667	Ameboidal-type cell migration	7/86	481/18866	0.006375514	0.08305588	0.067330711	GATA3/SASH1/TGFB2/SEMA3A/HDAC9/BMPR2/ITGB3	7
GO:0016569	Covalent chromatin modification	7/86	481/18866	0.006375514	0.08305588	0.067330711	GATA3/RSF1/MTHFR/HDAC9/ATF7IP/TET2/JMJD1C	7
GO:2000146	Negative regulation of cell motility	6/86	365/18866	0.006461198	0.083286412	0.067517597	GATA3/CLIC4/SEMA3A/PLCB1/PRKG1/TP53INP1	6
GO:2000243	Positive regulation of reproductive process	3/86	83/18866	0.006463081	0.083286412	0.067517597	SEMA3A/INHBB/PLCB1	3
GO:0003007	Heart morphogenesis	5/86	258/18866	0.006519717	0.083564546	0.067743071	GATA3/SMAD6/TGFB2/SOX4/BMPR2	5
GO:0021537	Telencephalon development	5/86	259/18866	0.006624687	0.084002275	0.068097923	SLC7A11/BCAN/SEMA3A/SLC38A2/PLCB1	5
GO:0050769	Positive regulation of neurogenesis	7/86	485/18866	0.006661076	0.084002275	0.068097923	CPEB3/PPP1R9A/SKIL/BDNF/SEMA3A/BMPR2/PACSIN1	7
GO:0007214	Gamma-aminobutyric acid signaling pathway	2/86	27/18866	0.006694812	0.084002275	0.068097923	GABRB3/BDNF	2
GO:0072337	Modified amino acid transport	2/86	27/18866	0.006694812	0.084002275	0.068097923	SLC7A11/SLC38A2	2
GO:0007611	Learning or memory	5/86	260/18866	0.006730839	0.084012142	0.068105922	CPEB3/SLC7A11/ATXN1/BDNF/PLCB1	5
GO:0014910	Regulation of smooth muscle cell migration	3/86	86/18866	0.007128822	0.086118398	0.069813396	SORL1/ATP7A/PRKG1	3
GO:0034109	Homotypic cell-cell adhesion	3/86	86/18866	0.007128822	0.086118398	0.069813396	SLC7A11/PRKG1/ITGB3	3
GO:0050772	Positive regulation of axonogenesis	3/86	86/18866	0.007128822	0.086118398	0.069813396	SKIL/BDNF/BMPR2	3
GO:1902903	Regulation of supramolecular fiber organization	6/86	373/18866	0.007157109	0.086118398	0.069813396	PPP1R9A/CGNL1/TTBK2/ARHGAP28/JMY/MAP2	6
GO:0003180	Aortic valve morphogenesis	2/86	28/18866	0.007188574	0.086118398	0.069813396	GATA3/SMAD6	2
GO:0031440	Regulation of mRNA 3′-end processing	2/86	28/18866	0.007188574	0.086118398	0.069813396	CPEB3/CCNT1	2
GO:0032800	Receptor biosynthetic process	2/86	28/18866	0.007188574	0.086118398	0.069813396	ITGAV/ITGB3	2
GO:0080111	DNA demethylation	2/86	28/18866	0.007188574	0.086118398	0.069813396	GATA3/TET2	2
GO:0032874	Positive regulation of stress-activated MAPK cascade	4/86	170/18866	0.007619707	0.090826908	0.073630433	SASH1/TGFB2/SEMA3A/PLCB1	4
GO:0042634	Regulation of hair cycle	2/86	29/18866	0.007698341	0.091302546	0.074016017	FST/TGFB2	2
GO:0022604	Regulation of cell morphogenesis	7/86	499/18866	0.007736206	0.091302546	0.074016017	PPP1R9A/SKIL/BDNF/SEMA3A/BMPR2/MAP2/NEDD9	7
GO:0045666	Positive regulation of neuron differentiation	6/86	380/18866	0.007809358	0.091370068	0.074070754	CPEB3/PPP1R9A/SKIL/BDNF/BMPR2/PACSIN1	6
GO:0002791	Regulation of peptide secretion	6/86	381/18866	0.007905929	0.091370068	0.074070754	SORL1/TGFB2/SOX4/HDAC9/MYO18A/INHBB	6
GO:0050714	Positive regulation of protein secretion	4/86	172/18866	0.007933559	0.091370068	0.074070754	SORL1/TGFB2/SOX4/MYO18A	4
GO:0070304	Positive regulation of stress-activated protein kinase signaling cascade	4/86	172/18866	0.007933559	0.091370068	0.074070754	SASH1/TGFB2/SEMA3A/PLCB1	4
GO:1990138	Neuron projection extension	4/86	172/18866	0.007933559	0.091370068	0.074070754	BDNF/SEMA3A/BMPR2/MAP2	4
GO:0045682	Regulation of epidermis development	3/86	91/18866	0.008325904	0.094971077	0.076989976	FST/TGFB2/TP63	3
GO:0051492	Regulation of stress fiber assembly	3/86	91/18866	0.008325904	0.094971077	0.076989976	PPP1R9A/CGNL1/ARHGAP28	3
GO:0060292	Long-term synaptic depression	2/86	31/18866	0.008765276	0.099506758	0.080666905	PPP1R9A/SLC24A1	2
GO:0045778	Positive regulation of ossification	3/86	94/18866	0.009097485	0.102722925	0.083274148	TGFB2/BMPR2/TP63	3
GO:1901796	Regulation of signal transduction by p53 class mediator	4/86	180/18866	0.009273809	0.102722925	0.083274148	NUAK1/JMY/TP53INP1/TP63	4
GO:0010743	Regulation of macrophage derived foam cell differentiation	2/86	32/18866	0.009322144	0.102722925	0.083274148	ITGAV/ITGB3	2
GO:0048841	Regulation of axon extension involved in axon guidance	2/86	32/18866	0.009322144	0.102722925	0.083274148	SEMA3A/BMPR2	2
GO:0061157	mRNA destabilization	2/86	32/18866	0.009322144	0.102722925	0.083274148	CPEB3/CNOT6L	2
GO:0030198	Extracellular matrix organization	6/86	395/18866	0.009350199	0.102722925	0.083274148	COL8A1/TGFB2/BCAN/ATP7A/ITGAV/ITGB3	6
GO:0050678	Regulation of epithelial cell proliferation	6/86	395/18866	0.009350199	0.102722925	0.083274148	GATA3/TGFB2/ATP7A/BMPR2/ITGB3/TP63	6
GO:0043062	Extracellular structure organization	6/86	396/18866	0.009460121	0.103453798	0.083866643	COL8A1/TGFB2/BCAN/ATP7A/ITGAV/ITGB3	6
GO:0001822	Kidney development	5/86	283/18866	0.009514131	0.103569356	0.083960322	GATA3/SMAD6/TGFB2/SOX4/BDNF	5
GO:0040013	Negative regulation of locomotion	6/86	397/18866	0.009570966	0.103635943	0.084014302	GATA3/CLIC4/SEMA3A/PLCB1/PRKG1/TP53INP1	6
GO:0090288	Negative regulation of cellular response to growth factor stimulus	4/86	182/18866	0.009630517	0.103635943	0.084014302	SORL1/GATA3/SKIL/SMAD6	4
GO:0007411	Axon guidance	5/86	284/18866	0.009650662	0.103635943	0.084014302	GATA3/ETV1/BDNF/SEMA3A/BMPR2	5
GO:0097485	Neuron projection guidance	5/86	285/18866	0.00978854	0.103806173	0.084152302	GATA3/ETV1/BDNF/SEMA3A/BMPR2	5
GO:0055001	Muscle cell development	4/86	183/18866	0.009812177	0.103806173	0.084152302	NEBL/PGM5/HDAC9/ANK2	4
GO:2000758	Positive regulation of peptidyllysine acetylation	2/86	33/18866	0.00989441	0.103806173	0.084152302	GATA3/SOX4	2
GO:0051271	Negative regulation of cellular component movement	6/86	400/18866	0.009909083	0.103806173	0.084152302	GATA3/CLIC4/SEMA3A/PLCB1/PRKG1/TP53INP1	6
GO:0030516	Regulation of axon extension	3/86	97/18866	0.009909621	0.103806173	0.084152302	SEMA3A/BMPR2/MAP2	3
GO:0043542	Endothelial cell migration	5/86	286/18866	0.009927772	0.103806173	0.084152302	GATA3/SASH1/HDAC9/BMPR2/ITGB3	5
GO:0007416	Synapse assembly	4/86	184/18866	0.009996053	0.104063714	0.084361082	PPP1R9A/GABRB3/BDNF/SLITRK6	4
GO:0001657	Ureteric bud development	3/86	98/18866	0.010189417	0.104705042	0.084880986	GATA3/SMAD6/BDNF	3
GO:0006835	Dicarboxylic acid transport	3/86	98/18866	0.010189417	0.104705042	0.084880986	SLC7A11/BDNF/SLC38A2	3
GO:0044728	DNA methylation or demethylation	3/86	98/18866	0.010189417	0.104705042	0.084880986	GATA3/ATF7IP/TET2	3
GO:0072163	Mesonephric epithelium development	3/86	99/18866	0.010473779	0.105981576	0.085915831	GATA3/SMAD6/BDNF	3
GO:0072164	Mesonephric tubule development	3/86	99/18866	0.010473779	0.105981576	0.085915831	GATA3/SMAD6/BDNF	3
GO:0035510	DNA dealkylation	2/86	34/18866	0.010481928	0.105981576	0.085915831	GATA3/TET2	2
GO:0018205	Peptidyl-lysine modification	6/86	405/18866	0.010491465	0.105981576	0.085915831	GATA3/RSF1/SOX4/ATP7A/HDAC9/TET2	6
GO:0072001	Renal system development	5/86	292/18866	0.010791921	0.108556703	0.088003403	GATA3/SMAD6/TGFB2/SOX4/BDNF	5
GO:0007369	Gastrulation	4/86	189/18866	0.010949043	0.108906117	0.088286661	COL8A1/ITGAV/BMPR2/ITGB3	4
GO:0007435	Salivary gland morphogenesis	2/86	35/18866	0.01108455	0.108906117	0.088286661	TGFB2/SEMA3A	2
GO:0035909	Aorta morphogenesis	2/86	35/18866	0.01108455	0.108906117	0.088286661	TGFB2/SOX4	2
GO:0050779	RNA destabilization	2/86	35/18866	0.01108455	0.108906117	0.088286661	CPEB3/CNOT6L	2
GO:0070306	Lens fiber cell differentiation	2/86	35/18866	0.01108455	0.108906117	0.088286661	SLC7A11/SKIL	2
GO:0006575	Cellular modified amino acid metabolic process	4/86	190/18866	0.011146431	0.108906117	0.088286661	SLC7A11/GATA3/MTHFR/CHAC1	4
GO:0030308	Negative regulation of cell growth	4/86	190/18866	0.011146431	0.108906117	0.088286661	TGFB2/SEMA3A/BMPR2/MAP2	4
GO:0048167	Regulation of synaptic plasticity	4/86	191/18866	0.011346106	0.110036081	0.089202686	CPEB3/PPP1R9A/SLC24A1/BDNF	4
GO:0110020	Regulation of actomyosin structure organization	3/86	102/18866	0.011354394	0.110036081	0.089202686	PPP1R9A/CGNL1/ARHGAP28	3
GO:0021953	Central nervous system neuron differentiation	4/86	192/18866	0.011548076	0.111010541	0.089992649	SOX4/SEMA3A/ATP7A/MAP2	4
GO:0044272	Sulfur compound biosynthetic process	4/86	192/18866	0.011548076	0.111010541	0.089992649	SLC7A11/BCAN/MTHFR/CHAC1	4
GO:0001823	Mesonephros development	3/86	103/18866	0.011657152	0.111591497	0.090463612	GATA3/SMAD6/BDNF	3
GO:0071634	Regulation of transforming growth factor beta production	2/86	36/18866	0.011702128	0.111591497	0.090463612	TGFB2/ITGAV	2
GO:0002793	Positive regulation of peptide secretion	4/86	193/18866	0.011752352	0.111623928	0.090489903	SORL1/TGFB2/SOX4/MYO18A	4
GO:0010639	Negative regulation of organelle organization	6/86	416/18866	0.011857924	0.112179729	0.090940473	PPP1R9A/CGNL1/USP30/TTBK2/ARHGAP28/MAP2	6
GO:0032231	Regulation of actin filament bundle assembly	3/86	104/18866	0.011964538	0.112740945	0.091395432	PPP1R9A/CGNL1/ARHGAP28	3
GO:0048846	Axon extension involved in axon guidance	2/86	37/18866	0.012334518	0.11495818	0.093192873	SEMA3A/BMPR2	2
GO:1902284	Neuron projection extension involved in neuron projection guidance	2/86	37/18866	0.012334518	0.11495818	0.093192873	SEMA3A/BMPR2	2
GO:0050890	Cognition	5/86	302/18866	0.012344503	0.11495818	0.093192873	CPEB3/SLC7A11/ATXN1/BDNF/PLCB1	5
GO:0001841	Neural tube formation	3/86	106/18866	0.012593245	0.11502795	0.093249434	TGFB2/SOX4/MTHFR	3
GO:0030038	Contractile actin filament bundle assembly	3/86	106/18866	0.012593245	0.11502795	0.093249434	PPP1R9A/CGNL1/ARHGAP28	3
GO:0032091	Negative regulation of protein binding	3/86	106/18866	0.012593245	0.11502795	0.093249434	SORL1/TTBK2/MAP2	3
GO:0034446	Substrate adhesion-dependent cell spreading	3/86	106/18866	0.012593245	0.11502795	0.093249434	ITGAV/NEDD9/ITGB3	3
GO:0043149	Stress fiber assembly	3/86	106/18866	0.012593245	0.11502795	0.093249434	PPP1R9A/CGNL1/ARHGAP28	3
GO:0051963	Regulation of synapse assembly	3/86	107/18866	0.012914585	0.116346145	0.094318051	PPP1R9A/BDNF/SLITRK6	3
GO:0007223	Wnt signaling pathway, calcium modulating pathway	2/86	38/18866	0.012981575	0.116346145	0.094318051	PLCB1/TNRC6C	2
GO:0010742	Macrophage derived foam cell differentiation	2/86	38/18866	0.012981575	0.116346145	0.094318051	ITGAV/ITGB3	2
GO:0071604	Transforming growth factor beta production	2/86	38/18866	0.012981575	0.116346145	0.094318051	TGFB2/ITGAV	2
GO:0090077	Foam cell differentiation	2/86	38/18866	0.012981575	0.116346145	0.094318051	ITGAV/ITGB3	2
GO:0007229	Integrin-mediated signaling pathway	3/86	108/18866	0.013240598	0.117782039	0.095482084	ITGAV/NEDD9/ITGB3	3
GO:0008593	Regulation of Notch signaling pathway	3/86	108/18866	0.013240598	0.117782039	0.095482084	TGFB2/CHAC1/TP63	3
GO:0001662	Behavioral fear response	2/86	39/18866	0.013643155	0.120019487	0.097295911	FBXL20/BDNF	2
GO:0007431	Salivary gland development	2/86	39/18866	0.013643155	0.120019487	0.097295911	TGFB2/SEMA3A	2
GO:0031111	Negative regulation of microtubule polymerization or depolymerization	2/86	39/18866	0.013643155	0.120019487	0.097295911	TTBK2/MAP2	2
GO:0090100	Positive regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	3/86	110/18866	0.013906677	0.121887936	0.098810602	TGFB2/INHBB/BMPR2	3
GO:0050808	Synapse organization	6/86	433/18866	0.01421063	0.122354017	0.099188438	PPP1R9A/SLC7A11/GABRB3/BCAN/BDNF/SLITRK6	6
GO:1903532	Positive regulation of secretion by cell	5/86	313/18866	0.014220651	0.122354017	0.099188438	SORL1/TGFB2/SOX4/MYO18A/INHBB	5
GO:0000096	Sulfur amino acid metabolic process	2/86	40/18866	0.014319115	0.122354017	0.099188438	SLC7A11/MTHFR	2
GO:0002209	Behavioral defense response	2/86	40/18866	0.014319115	0.122354017	0.099188438	FBXL20/BDNF	2
GO:0010719	Negative regulation of epithelial to mesenchymal transition	2/86	40/18866	0.014319115	0.122354017	0.099188438	GATA3/TGFB2	2
GO:0042417	Dopamine metabolic process	2/86	40/18866	0.014319115	0.122354017	0.099188438	TGFB2/ATP7A	2
GO:0043902	Positive regulation of multi-organism process	2/86	40/18866	0.014319115	0.122354017	0.099188438	INHBB/PLCB1	2
GO:0098656	Anion transmembrane transport	5/86	315/18866	0.014581278	0.123355537	0.100000338	SLC7A11/CLIC4/SLC24A1/GABRB3/SLC38A2	5
GO:0010927	Cellular component assembly involved in morphogenesis	3/86	112/18866	0.014591553	0.123355537	0.100000338	NEBL/PGM5/ANK2	3
GO:0099565	Chemical synaptic transmission, postsynaptic	3/86	112/18866	0.014591553	0.123355537	0.100000338	PPP1R9A/GABRB3/BDNF	3
GO:0007009	Plasma membrane organization	3/86	113/18866	0.014941059	0.125112608	0.101424739	TGFB2/ANK2/PACSIN1	3
GO:0042596	Fear response	2/86	41/18866	0.015009315	0.125112608	0.101424739	FBXL20/BDNF	2
GO:0050434	Positive regulation of viral transcription	2/86	41/18866	0.015009315	0.125112608	0.101424739	CCNT1/RSF1	2
GO:2000826	Regulation of heart morphogenesis	2/86	41/18866	0.015009315	0.125112608	0.101424739	TGFB2/BMPR2	2
GO:0043200	Response to amino acid	3/86	114/18866	0.015295288	0.127052153	0.102997065	CPEB3/MTHFR/ATP7A	3
GO:0043393	Regulation of protein binding	4/86	211/18866	0.015833518	0.13061283	0.105883591	SORL1/BDNF/TTBK2/MAP2	4
GO:0050679	Positive regulation of epithelial cell proliferation	4/86	211/18866	0.015833518	0.13061283	0.105883591	ATP7A/BMPR2/ITGB3/TP63	4
GO:0030278	Regulation of ossification	4/86	212/18866	0.016083232	0.131760911	0.106814303	SMAD6/TGFB2/BMPR2/TP63	4
GO:1901215	Negative regulation of neuron death	4/86	212/18866	0.016083232	0.131760911	0.106814303	SORL1/SLC7A11/GABRB3/BDNF	4
GO:0030517	Negative regulation of axon extension	2/86	43/18866	0.016431868	0.133243447	0.108016147	SEMA3A/MAP2	2
GO:0040019	Positive regulation of embryonic development	2/86	43/18866	0.016431868	0.133243447	0.108016147	GATA3/PLCB1	2
GO:0060119	Inner ear receptor cell development	2/86	43/18866	0.016431868	0.133243447	0.108016147	GABRB3/SLITRK6	2
GO:0043523	Regulation of neuron apoptotic process	4/86	214/18866	0.016590079	0.134070337	0.108686479	GATA3/GABRB3/TGFB2/BDNF	4
GO:0071496	Cellular response to external stimulus	5/86	326/18866	0.016675122	0.134302338	0.108874555	NUAK1/SLC38A2/GABARAPL1/INHBB/BMPR2	5
GO:0046660	Female sex differentiation	3/86	119/18866	0.017137505	0.135942997	0.110204584	FST/INHBB/TP63	3
GO:0045684	Positive regulation of epidermis development	2/86	44/18866	0.017163944	0.135942997	0.110204584	FST/TGFB2	2
GO:0060999	Positive regulation of dendritic spine development	2/86	44/18866	0.017163944	0.135942997	0.110204584	CPEB3/PPP1R9A	2
GO:1901985	Positive regulation of protein acetylation	2/86	44/18866	0.017163944	0.135942997	0.110204584	GATA3/SOX4	2
GO:1902667	Regulation of axon guidance	2/86	44/18866	0.017163944	0.135942997	0.110204584	SEMA3A/BMPR2	2
GO:0006304	DNA modification	3/86	120/18866	0.017520203	0.137848726	0.111749497	GATA3/ATF7IP/TET2	3
GO:0051588	Regulation of neurotransmitter transport	3/86	120/18866	0.017520203	0.137848726	0.111749497	PPP1R9A/FBXL20/ITGB3	3
GO:0006338	Chromatin remodeling	4/86	218/18866	0.017633653	0.138177114	0.11201571	GATA3/RSF1/ATF7IP/TP63	4
GO:0060562	Epithelial tube morphogenesis	5/86	331/18866	0.017689868	0.138177114	0.11201571	GATA3/CLIC4/TGFB2/SOX4/MTHFR	5
GO:0002065	Columnar/cuboidal epithelial cell differentiation	3/86	121/18866	0.017907664	0.138177114	0.11201571	SOX4/SLITRK6/TP63	3
GO:0001974	Blood vessel remodeling	2/86	45/18866	0.017909701	0.138177114	0.11201571	ATP7A/BMPR2	2
GO:0003197	Endocardial cushion development	2/86	45/18866	0.017909701	0.138177114	0.11201571	TGFB2/BMPR2	2
GO:0014047	Glutamate secretion	2/86	45/18866	0.017909701	0.138177114	0.11201571	BDNF/SLC38A2	2
GO:0007163	Establishment or maintenance of cell polarity	4/86	220/18866	0.01817049	0.139736926	0.1132802	GATA3/CLIC4/MYO18A/MAP2	4
GO:0097237	Cellular response to toxic substance	3/86	122/18866	0.018299893	0.140279566	0.1137201	PPP1R9A/ATP7A/TP53INP1	3
GO:0032570	Response to progesterone	2/86	46/18866	0.018669004	0.142194587	0.115272545	NCOA2/TGFB2	2
GO:0035987	Endodermal cell differentiation	2/86	46/18866	0.018669004	0.142194587	0.115272545	COL8A1/ITGAV	2
GO:0009306	Protein secretion	6/86	462/18866	0.018947479	0.143856018	0.116619414	SORL1/TGFB2/SOX4/HDAC9/MYO18A/INHBB	6
GO:0022612	Gland morphogenesis	3/86	124/18866	0.019098668	0.144306981	0.116984995	TGFB2/SEMA3A/TP63	3
GO:0035592	Establishment of protein localization to extracellular region	6/86	463/18866	0.019127939	0.144306981	0.116984995	SORL1/TGFB2/SOX4/HDAC9/MYO18A/INHBB	6
GO:0006378	mRNA polyadenylation	2/86	47/18866	0.019441716	0.144389565	0.117051943	CPEB3/CCNT1	2
GO:0032369	Negative regulation of lipid transport	2/86	47/18866	0.019441716	0.144389565	0.117051943	ITGAV/ITGB3	2
GO:0060986	Endocrine hormone secretion	2/86	47/18866	0.019441716	0.144389565	0.117051943	GATA3/INHBB	2
GO:1904738	Vascular associated smooth muscle cell migration	2/86	47/18866	0.019441716	0.144389565	0.117051943	ATP7A/PRKG1	2
GO:1904752	Regulation of vascular associated smooth muscle cell migration	2/86	47/18866	0.019441716	0.144389565	0.117051943	ATP7A/PRKG1	2
GO:0016570	Histone modification	6/86	468/18866	0.02004796	0.148094346	0.120055289	GATA3/RSF1/MTHFR/HDAC9/TET2/JMJD1C	6
GO:0009101	Glycoprotein biosynthetic process	5/86	342/18866	0.020064796	0.148094346	0.120055289	BCAN/ATP7A/BMPR2/PLCB1/TET2	5
GO:0043631	RNA polyadenylation	2/86	48/18866	0.020227701	0.148835926	0.120656465	CPEB3/CCNT1	2
GO:0007596	Blood coagulation	5/86	343/18866	0.020290572	0.14883915	0.120659078	SLC7A11/GATA3/PRKG1/JMJD1C/ITGB3	5
GO:0071692	Protein localization to extracellular region	6/86	470/18866	0.0204243	0.149360526	0.12108174	SORL1/TGFB2/SOX4/HDAC9/MYO18A/INHBB	6
GO:1903311	Regulation of mRNA metabolic process	5/86	344/18866	0.020518013	0.149586983	0.121265322	CPEB3/CCNT1/MBNL2/TNRC6C/CNOT6L	5
GO:0050807	Regulation of synapse organization	4/86	229/18866	0.020712003	0.150540902	0.122038633	PPP1R9A/SLC7A11/BDNF/SLITRK6	4
GO:0015695	Organic cation transport	2/86	49/18866	0.021026827	0.151902896	0.123142758	SLC38A2/ITGB3	2
GO:0042398	Cellular modified amino acid biosynthetic process	2/86	49/18866	0.021026827	0.151902896	0.123142758	SLC7A11/CHAC1	2
GO:0032271	Regulation of protein polymerization	4/86	231/18866	0.021305014	0.153447596	0.124394996	PPP1R9A/ARHGAP28/JMY/MAP2	4
GO:0007599	Hemostasis	5/86	348/18866	0.021444515	0.153987119	0.12483237	SLC7A11/GATA3/PRKG1/JMJD1C/ITGB3	5
GO:0050817	Coagulation	5/86	349/18866	0.021680346	0.154492818	0.125242323	SLC7A11/GATA3/PRKG1/JMJD1C/ITGB3	5
GO:0008544	Epidermis development	6/86	477/18866	0.02177946	0.154492818	0.125242323	FST/CLIC4/TGFB2/ATP7A/SLITRK6/TP63	6
GO:0008038	Neuron recognition	2/86	50/18866	0.02183896	0.154492818	0.125242323	BDNF/SEMA3A	2
GO:0021695	Cerebellar cortex development	2/86	50/18866	0.02183896	0.154492818	0.125242323	ATP7A/TTBK2	2
GO:0043616	Keratinocyte proliferation	2/86	50/18866	0.02183896	0.154492818	0.125242323	FST/TP63	2
GO:0030336	Negative regulation of cell migration	5/86	350/18866	0.021917868	0.1545923	0.12532297	CLIC4/SEMA3A/PLCB1/PRKG1/TP53INP1	5
GO:0045667	Regulation of osteoblast differentiation	3/86	131/18866	0.022045008	0.155030383	0.12567811	SMAD6/BMPR2/TP63	3
GO:0001101	Response to acid chemical	3/86	132/18866	0.022485065	0.155708635	0.126227947	CPEB3/MTHFR/ATP7A	3
GO:0042476	Odontogenesis	3/86	132/18866	0.022485065	0.155708635	0.126227947	FST/TGFB2/TP63	3
GO:0045444	Fat cell differentiation	4/86	235/18866	0.022522167	0.155708635	0.126227947	GATA3/SMAD6/INHBB/PLCB1	4
GO:0048638	Regulation of developmental growth	5/86	353/18866	0.022640619	0.155708635	0.126227947	BDNF/SEMA3A/BMPR2/PLCB1/MAP2	5
GO:0021545	Cranial nerve development	2/86	51/18866	0.022663967	0.155708635	0.126227947	SEMA3A/SLITRK6	2
GO:0021879	Forebrain neuron differentiation	2/86	51/18866	0.022663967	0.155708635	0.126227947	SEMA3A/ATP7A	2
GO:0035272	Exocrine system development	2/86	51/18866	0.022663967	0.155708635	0.126227947	TGFB2/SEMA3A	2
GO:0043277	Apoptotic cell clearance	2/86	51/18866	0.022663967	0.155708635	0.126227947	ITGAV/ITGB3	2
GO:0060560	Developmental growth involved in morphogenesis	4/86	236/18866	0.022832971	0.156325812	0.126728272	BDNF/SEMA3A/BMPR2/MAP2	4
GO:0051222	Positive regulation of protein transport	5/86	354/18866	0.022884945	0.156325812	0.126728272	SORL1/TGFB2/SOX4/MYO18A/TP63	5
GO:0032872	Regulation of stress-activated MAPK cascade	4/86	237/18866	0.023146391	0.157210815	0.127445716	SASH1/TGFB2/SEMA3A/PLCB1	4
GO:0048588	Developmental cell growth	4/86	237/18866	0.023146391	0.157210815	0.127445716	BDNF/SEMA3A/BMPR2/MAP2	4
GO:0007498	Mesoderm development	3/86	134/18866	0.023379551	0.158271449	0.128305537	BMPR2/ITGB3/TP63	3
GO:0034249	Negative regulation of cellular amide metabolic process	4/86	238/18866	0.023462432	0.158271449	0.128305537	SORL1/CPEB3/TNRC6C/CNOT6L	4
GO:0010883	Regulation of lipid storage	2/86	52/18866	0.023501717	0.158271449	0.128305537	ITGAV/ITGB3	2
GO:0050803	Regulation of synapse structure or activity	4/86	240/18866	0.024102395	0.161152503	0.130641115	PPP1R9A/SLC7A11/BDNF/SLITRK6	4
GO:0070302	Regulation of stress-activated protein kinase signaling cascade	4/86	240/18866	0.024102395	0.161152503	0.130641115	SASH1/TGFB2/SEMA3A/PLCB1	4
GO:0031589	Cell-substrate adhesion	5/86	359/18866	0.024132317	0.161152503	0.130641115	COL8A1/SMAD6/ITGAV/NEDD9/ITGB3	5
GO:0042073	Intraciliary transport	2/86	53/18866	0.02435208	0.162165805	0.131462566	RABL2B/LCA5	2
GO:0006749	Glutathione metabolic process	2/86	54/18866	0.025214926	0.167052167	0.135423781	SLC7A11/CHAC1	2
GO:0046330	Positive regulation of JNK cascade	3/86	138/18866	0.025225998	0.167052167	0.135423781	SASH1/SEMA3A/PLCB1	3
GO:0001706	Endoderm formation	2/86	55/18866	0.026090127	0.171820063	0.139288959	COL8A1/ITGAV	2
GO:0030199	Collagen fibril organization	2/86	55/18866	0.026090127	0.171820063	0.139288959	TGFB2/ATP7A	2
GO:0008584	Male gonad development	3/86	141/18866	0.026661088	0.174456189	0.141425982	GATA3/TGFB2/SEMA3A	3
GO:0030010	Establishment of cell polarity	3/86	141/18866	0.026661088	0.174456189	0.141425982	GATA3/MYO18A/MAP2	3
GO:0006977	DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest	2/86	56/18866	0.026977555	0.174456189	0.141425982	SOX4/CNOT6L	2
GO:0044273	Sulfur compound catabolic process	2/86	56/18866	0.026977555	0.174456189	0.141425982	BCAN/CHAC1	2
GO:0060563	Neuroepithelial cell differentiation	2/86	56/18866	0.026977555	0.174456189	0.141425982	SOX4/SLITRK6	2
GO:1904951	Positive regulation of establishment of protein localization	5/86	370/18866	0.027029446	0.174456189	0.141425982	SORL1/TGFB2/SOX4/MYO18A/TP63	5
GO:0031333	Negative regulation of protein-containing complex assembly	3/86	142/18866	0.027149013	0.174456189	0.141425982	SORL1/SMAD6/MAP2	3
GO:0046546	Development of primary male sexual characteristics	3/86	142/18866	0.027149013	0.174456189	0.141425982	GATA3/TGFB2/SEMA3A	3
GO:0072073	Kidney epithelium development	3/86	142/18866	0.027149013	0.174456189	0.141425982	GATA3/SMAD6/BDNF	3
GO:0016571	Histone methylation	3/86	143/18866	0.027641714	0.176752565	0.143287579	GATA3/MTHFR/TET2	3
GO:0045747	Positive regulation of Notch signaling pathway	2/86	57/18866	0.027877082	0.176752565	0.143287579	TGFB2/TP63	2
GO:0051568	Histone H3-K4 methylation	2/86	57/18866	0.027877082	0.176752565	0.143287579	GATA3/TET2	2
GO:0072431	Signal transduction involved in mitotic G1 DNA damage checkpoint	2/86	57/18866	0.027877082	0.176752565	0.143287579	SOX4/CNOT6L	2
GO:1902400	Intracellular signal transduction involved in G1 DNA damage checkpoint	2/86	57/18866	0.027877082	0.176752565	0.143287579	SOX4/CNOT6L	2
GO:0060078	Regulation of postsynaptic membrane potential	3/86	144/18866	0.028139189	0.177941187	0.144251156	PPP1R9A/GABRB3/BDNF	3
GO:0045926	Negative regulation of growth	4/86	254/18866	0.02887904	0.181656023	0.147262653	TGFB2/SEMA3A/BMPR2/MAP2	4
GO:2000027	Regulation of animal organ morphogenesis	4/86	254/18866	0.02887904	0.181656023	0.147262653	GATA3/TGFB2/BDNF/BMPR2	4
GO:0048813	Dendrite morphogenesis	3/86	146/18866	0.029148446	0.182868148	0.148245284	PPP1R9A/SEMA3A/MAP2	3
GO:0050707	Regulation of cytokine secretion	2/86	59/18866	0.029711935	0.183505836	0.148762237	SORL1/HDAC9	2
GO:0051058	Negative regulation of small GTPase mediated signal transduction	2/86	59/18866	0.029711935	0.183505836	0.148762237	CGNL1/TGFB2	2
GO:0060113	Inner ear receptor cell differentiation	2/86	59/18866	0.029711935	0.183505836	0.148762237	GABRB3/SLITRK6	2
GO:0072413	Signal transduction involved in mitotic cell cycle checkpoint	2/86	59/18866	0.029711935	0.183505836	0.148762237	SOX4/CNOT6L	2
GO:1902402	Signal transduction involved in mitotic DNA damage checkpoint	2/86	59/18866	0.029711935	0.183505836	0.148762237	SOX4/CNOT6L	2
GO:1902403	Signal transduction involved in mitotic DNA integrity checkpoint	2/86	59/18866	0.029711935	0.183505836	0.148762237	SOX4/CNOT6L	2
GO:0042093	T-helper cell differentiation	2/86	60/18866	0.03064701	0.187339672	0.151870204	GATA3/ATP7A	2
GO:0048747	Muscle fiber development	2/86	60/18866	0.03064701	0.187339672	0.151870204	NEBL/HDAC9	2
GO:0061098	Positive regulation of protein tyrosine kinase activity	2/86	60/18866	0.03064701	0.187339672	0.151870204	BDNF/NEDD9	2
GO:0097755	Positive regulation of blood vessel diameter	2/86	60/18866	0.03064701	0.187339672	0.151870204	BMPR2/PRKG1	2
GO:0035107	Appendage morphogenesis	3/86	150/18866	0.031224077	0.189410176	0.153548695	TGFB2/SOX4/TP63	3
GO:0035108	Limb morphogenesis	3/86	150/18866	0.031224077	0.189410176	0.153548695	TGFB2/SOX4/TP63	3
GO:0060041	Retina development in camera-type eye	3/86	150/18866	0.031224077	0.189410176	0.153548695	CLIC4/TGFB2/BMPR2	3
GO:0021872	Forebrain generation of neurons	2/86	61/18866	0.031593687	0.190681897	0.154579637	SEMA3A/ATP7A	2
GO:2000756	Regulation of peptidyl-lysine acetylation	2/86	61/18866	0.031593687	0.190681897	0.154579637	GATA3/SOX4	2
GO:0050684	Regulation of mRNA processing	3/86	152/18866	0.032290377	0.194394591	0.157589398	CPEB3/CCNT1/MBNL2	3
GO:0002294	CD4-positive, alpha-beta T cell differentiation involved in immune response	2/86	62/18866	0.032551842	0.194858921	0.157965815	GATA3/ATP7A	2
GO:0034113	Heterotypic cell-cell adhesion	2/86	62/18866	0.032551842	0.194858921	0.157965815	ITGAV/ITGB3	2
GO:0048863	Stem cell differentiation	4/86	264/18866	0.032612714	0.194858921	0.157965815	GATA3/TGFB2/SEMA3A/TP63	4
GO:0042692	Muscle cell differentiation	5/86	390/18866	0.032848287	0.195775793	0.158709094	NEBL/PGM5/BDNF/HDAC9/ANK2	5
GO:0002287	Alpha-beta T cell activation involved in immune response	2/86	63/18866	0.033521355	0.197809181	0.160357496	GATA3/ATP7A	2
GO:0002293	Alpha-beta T cell differentiation involved in immune response	2/86	63/18866	0.033521355	0.197809181	0.160357496	GATA3/ATP7A	2
GO:0010830	Regulation of myotube differentiation	2/86	63/18866	0.033521355	0.197809181	0.160357496	BDNF/HDAC9	2
GO:0031571	Mitotic G1 DNA damage checkpoint	2/86	63/18866	0.033521355	0.197809181	0.160357496	SOX4/CNOT6L	2
GO:0050773	Regulation of dendrite development	3/86	155/18866	0.033925312	0.199698629	0.16188921	CPEB3/PPP1R9A/PACSIN1	3
GO:0006865	Amino acid transport	3/86	156/18866	0.03447973	0.200587288	0.162609617	SLC7A11/BDNF/SLC38A2	3
GO:0043484	Regulation of RNA splicing	3/86	156/18866	0.03447973	0.200587288	0.162609617	MBNL2/SLC38A2/AHNAK2	3
GO:0030166	Proteoglycan biosynthetic process	2/86	64/18866	0.034502103	0.200587288	0.162609617	BCAN/BMPR2	2
GO:0044783	G1 DNA damage checkpoint	2/86	64/18866	0.034502103	0.200587288	0.162609617	SOX4/CNOT6L	2
GO:0044819	Mitotic G1/S transition checkpoint	2/86	64/18866	0.034502103	0.200587288	0.162609617	SOX4/CNOT6L	2
GO:0090596	Sensory organ morphogenesis	4/86	269/18866	0.034581114	0.200587288	0.162609617	COL8A1/GATA3/BDNF/SLITRK6	4
GO:0045787	Positive regulation of cell cycle	5/86	396/18866	0.034735534	0.200993965	0.162939297	CCNT1/TGFB2/SOX4/PLCB1/CNOT6L	5
GO:0046782	Regulation of viral transcription	2/86	65/18866	0.035493968	0.204390387	0.165692666	CCNT1/RSF1	2
GO:1905953	Negative regulation of lipid localization	2/86	65/18866	0.035493968	0.204390387	0.165692666	ITGAV/ITGB3	2
GO:0030168	Platelet activation	3/86	158/18866	0.035602685	0.20452241	0.165799693	SLC7A11/PRKG1/ITGB3	3
GO:0032922	Circadian regulation of gene expression	2/86	66/18866	0.03649683	0.208154171	0.168743844	AHR/NCOA2	2
GO:0034394	Protein localization to cell surface	2/86	66/18866	0.03649683	0.208154171	0.168743844	BDNF/ANK2	2
GO:0045669	Positive regulation of osteoblast differentiation	2/86	66/18866	0.03649683	0.208154171	0.168743844	BMPR2/TP63	2
GO:0045927	Positive regulation of growth	4/86	274/18866	0.03661755	0.208344248	0.168897933	TGFB2/BDNF/BMPR2/PLCB1	4
GO:0010970	Transport along microtubule	3/86	161/18866	0.037322311	0.211407097	0.171380886	RABL2B/LCA5/MAP2	3
GO:0030239	Myofibril assembly	2/86	67/18866	0.037510571	0.211407097	0.171380886	NEBL/PGM5	2
GO:0031060	Regulation of histone methylation	2/86	67/18866	0.037510571	0.211407097	0.171380886	GATA3/MTHFR	2
GO:0051965	Positive regulation of synapse assembly	2/86	67/18866	0.037510571	0.211407097	0.171380886	BDNF/SLITRK6	2
GO:0032970	Regulation of actin filament-based process	5/86	405/18866	0.037690922	0.211922541	0.17179874	PPP1R9A/CGNL1/ARHGAP28/ANK2/JMY	5
GO:0110053	Regulation of actin filament organization	4/86	278/18866	0.038295803	0.213645618	0.173195582	PPP1R9A/CGNL1/ARHGAP28/JMY	4
GO:0021915	Neural tube development	3/86	163/18866	0.038492103	0.213645618	0.173195582	TGFB2/SOX4/MTHFR	3
GO:0072577	Endothelial cell apoptotic process	2/86	68/18866	0.038535074	0.213645618	0.173195582	GATA3/BMPR2	2
GO:0098840	Protein transport along microtubule	2/86	68/18866	0.038535074	0.213645618	0.173195582	RABL2B/LCA5	2
GO:0099118	Microtubule-based protein transport	2/86	68/18866	0.038535074	0.213645618	0.173195582	RABL2B/LCA5	2
GO:1904888	Cranial skeletal system development	2/86	68/18866	0.038535074	0.213645618	0.173195582	TGFB2/TP63	2
GO:0001764	Neuron migration	3/86	164/18866	0.039083988	0.215208675	0.174462702	GATA3/SEMA3A/PRKG1	3
GO:0046661	Male sex differentiation	3/86	164/18866	0.039083988	0.215208675	0.174462702	GATA3/TGFB2/SEMA3A	3
GO:0071230	Cellular response to amino acid stimulus	2/86	69/18866	0.039570221	0.215208675	0.174462702	CPEB3/ATP7A	2
GO:1903317	Regulation of protein maturation	2/86	69/18866	0.039570221	0.215208675	0.174462702	SOX4/CHAC1	2
GO:1903531	Negative regulation of secretion by cell	3/86	166/18866	0.040281693	0.215208675	0.174462702	PPP1R9A/HDAC9/INHBB	3
GO:2001233	Regulation of apoptotic signaling pathway	5/86	413/18866	0.040444458	0.215208675	0.174462702	SKIL/BDNF/ITGAV/INHBB/TP63	5
GO:0009880	Embryonic pattern specification	2/86	70/18866	0.040615897	0.215208675	0.174462702	SMAD6/SEMA3A	2
GO:0050771	Negative regulation of axonogenesis	2/86	70/18866	0.040615897	0.215208675	0.174462702	SEMA3A/MAP2	2
GO:0009100	Glycoprotein metabolic process	5/86	415/18866	0.041151564	0.215208675	0.174462702	BCAN/ATP7A/BMPR2/PLCB1/TET2	5
GO:0002292	T cell differentiation involved in immune response	2/86	71/18866	0.041671986	0.215208675	0.174462702	GATA3/ATP7A	2
GO:0051403	Stress-activated MAPK cascade	4/86	286/18866	0.041783498	0.215208675	0.174462702	SASH1/TGFB2/SEMA3A/PLCB1	4
GO:0055002	Striated muscle cell development	3/86	169/18866	0.042112957	0.215208675	0.174462702	NEBL/PGM5/HDAC9	3
GO:2000241	Regulation of reproductive process	3/86	170/18866	0.042732596	0.215208675	0.174462702	SEMA3A/INHBB/PLCB1	3
GO:0050663	Cytokine secretion	2/86	72/18866	0.042738376	0.215208675	0.174462702	SORL1/HDAC9	2
GO:0001558	Regulation of cell growth	5/86	420/18866	0.042952231	0.215208675	0.174462702	TGFB2/BDNF/SEMA3A/BMPR2/MAP2	5
GO:0030307	Positive regulation of cell growth	3/86	171/18866	0.043356828	0.215208675	0.174462702	TGFB2/BDNF/BMPR2	3
GO:0060485	Mesenchyme development	4/86	290/18866	0.043592995	0.215208675	0.174462702	GATA3/TGFB2/SEMA3A/BMPR2	4
GO:0097193	Intrinsic apoptotic signaling pathway	4/86	290/18866	0.043592995	0.215208675	0.174462702	SKIL/CHAC1/JMY/TP63	4
GO:0015807	l-amino acid transport	2/86	73/18866	0.043814951	0.215208675	0.174462702	SLC7A11/SLC38A2	2
GO:0072401	Signal transduction involved in DNA integrity checkpoint	2/86	73/18866	0.043814951	0.215208675	0.174462702	SOX4/CNOT6L	2
GO:0072422	Signal transduction involved in DNA damage checkpoint	2/86	73/18866	0.043814951	0.215208675	0.174462702	SOX4/CNOT6L	2
GO:0002244	Hematopoietic progenitor cell differentiation	3/86	172/18866	0.043985644	0.215208675	0.174462702	FST/GATA3/SOX4	3
GO:0018394	Peptidyl-lysine acetylation	3/86	172/18866	0.043985644	0.215208675	0.174462702	GATA3/RSF1/SOX4	3
GO:0021543	Pallium development	3/86	173/18866	0.044619032	0.215208675	0.174462702	BCAN/SLC38A2/PLCB1	3
GO:0002524	Hypersensitivity	1/86	10/18866	0.044671283	0.215208675	0.174462702	GATA3	1
GO:0003149	Membranous septum morphogenesis	1/86	10/18866	0.044671283	0.215208675	0.174462702	TGFB2	1
GO:0003211	Cardiac ventricle formation	1/86	10/18866	0.044671283	0.215208675	0.174462702	SOX4	1
GO:0010603	Regulation of cytoplasmic mRNA processing body assembly	1/86	10/18866	0.044671283	0.215208675	0.174462702	CNOT6L	1
GO:0021562	Vestibulocochlear nerve development	1/86	10/18866	0.044671283	0.215208675	0.174462702	SLITRK6	1
GO:0021859	Pyramidal neuron differentiation	1/86	10/18866	0.044671283	0.215208675	0.174462702	ATP7A	1
GO:0032025	Response to cobalt ion	1/86	10/18866	0.044671283	0.215208675	0.174462702	ATP7A	1
GO:0032926	Negative regulation of activin receptor signaling pathway	1/86	10/18866	0.044671283	0.215208675	0.174462702	FST	1
GO:0035860	Glial cell-derived neurotrophic factor receptor signaling pathway	1/86	10/18866	0.044671283	0.215208675	0.174462702	GATA3	1
GO:0035871	Protein K11-linked deubiquitination	1/86	10/18866	0.044671283	0.215208675	0.174462702	USP30	1
GO:0035999	Tetrahydrofolate interconversion	1/86	10/18866	0.044671283	0.215208675	0.174462702	MTHFR	1
GO:0042428	Serotonin metabolic process	1/86	10/18866	0.044671283	0.215208675	0.174462702	ATP7A	1
GO:0044557	Relaxation of smooth muscle	1/86	10/18866	0.044671283	0.215208675	0.174462702	PRKG1	1
GO:0045793	Positive regulation of cell size	1/86	10/18866	0.044671283	0.215208675	0.174462702	ATP7A	1
GO:0048251	Elastic fiber assembly	1/86	10/18866	0.044671283	0.215208675	0.174462702	ATP7A	1
GO:0051541	Elastin metabolic process	1/86	10/18866	0.044671283	0.215208675	0.174462702	ATP7A	1
GO:0060513	Prostatic bud formation	1/86	10/18866	0.044671283	0.215208675	0.174462702	TP63	1
GO:0060600	Dichotomous subdivision of an epithelial terminal unit	1/86	10/18866	0.044671283	0.215208675	0.174462702	SEMA3A	1
GO:0086070	SA node cell to atrial cardiac muscle cell communication	1/86	10/18866	0.044671283	0.215208675	0.174462702	ANK2	1
GO:0090527	Actin filament reorganization	1/86	10/18866	0.044671283	0.215208675	0.174462702	NEDD9	1
GO:1902946	Protein localization to early endosome	1/86	10/18866	0.044671283	0.215208675	0.174462702	SORL1	1
GO:1904672	Regulation of somatic stem cell population maintenance	1/86	10/18866	0.044671283	0.215208675	0.174462702	TP63	1
GO:1904684	Negative regulation of metalloendopeptidase activity	1/86	10/18866	0.044671283	0.215208675	0.174462702	SORL1	1
GO:2000018	Regulation of male gonad development	1/86	10/18866	0.044671283	0.215208675	0.174462702	SEMA3A	1
GO:2000271	Positive regulation of fibroblast apoptotic process	1/86	10/18866	0.044671283	0.215208675	0.174462702	TP63	1
GO:0043588	Skin development	5/86	425/18866	0.044800039	0.215208675	0.174462702	FST/CLIC4/TGFB2/ATP7A/TP63	5
GO:0072395	Signal transduction involved in cell cycle checkpoint	2/86	74/18866	0.0449016	0.215208675	0.174462702	SOX4/CNOT6L	2
GO:0030833	Regulation of actin filament polymerization	3/86	174/18866	0.045256984	0.215208675	0.174462702	PPP1R9A/ARHGAP28/JMY	3
GO:0010921	Regulation of phosphatase activity	3/86	175/18866	0.045899487	0.215208675	0.174462702	NUAK1/SYTL2/TGFB2	3
GO:0050768	Negative regulation of neurogenesis	4/86	295/18866	0.045916409	0.215208675	0.174462702	SORL1/BDNF/SEMA3A/MAP2	4
GO:0051146	Striated muscle cell differentiation	4/86	295/18866	0.045916409	0.215208675	0.174462702	NEBL/PGM5/BDNF/HDAC9	4
GO:0001707	Mesoderm formation	2/86	75/18866	0.045998211	0.215208675	0.174462702	BMPR2/ITGB3	2
GO:0035019	Somatic stem cell population maintenance	2/86	75/18866	0.045998211	0.215208675	0.174462702	SOX4/TP63	2
GO:0043627	Response to estrogen	2/86	75/18866	0.045998211	0.215208675	0.174462702	GATA3/SMAD6	2
GO:1901983	Regulation of protein acetylation	2/86	75/18866	0.045998211	0.215208675	0.174462702	GATA3/SOX4	2
GO:0033555	Multicellular organismal response to stress	2/86	76/18866	0.047104673	0.215208675	0.174462702	FBXL20/BDNF	2
GO:0071229	Cellular response to acid chemical	2/86	76/18866	0.047104673	0.215208675	0.174462702	CPEB3/ATP7A	2
GO:0030324	Lung development	3/86	177/18866	0.047198109	0.215208675	0.174462702	SLC7A11/ATP7A/BMPR2	3
GO:0048771	Tissue remodeling	3/86	178/18866	0.047854205	0.215208675	0.174462702	ATP7A/BMPR2/ITGB3	3
GO:0007422	Peripheral nervous system development	2/86	77/18866	0.048220875	0.215208675	0.174462702	ETV1/BDNF	2
GO:0048332	Mesoderm morphogenesis	2/86	77/18866	0.048220875	0.215208675	0.174462702	BMPR2/ITGB3	2
GO:0034329	Cell junction assembly	5/86	434/18866	0.048245354	0.215208675	0.174462702	PPP1R9A/GABRB3/BDNF/ANK2/SLITRK6	5
GO:0031098	Stress-activated protein kinase signaling cascade	4/86	300/18866	0.048308144	0.215208675	0.174462702	SASH1/TGFB2/SEMA3A/PLCB1	4
GO:0051258	Protein polymerization	4/86	300/18866	0.048308144	0.215208675	0.174462702	PPP1R9A/ARHGAP28/JMY/MAP2	4
GO:0002182	Cytoplasmic translational elongation	1/86	11/18866	0.049028425	0.215208675	0.174462702	CPEB3	1
GO:0002328	Pro-B cell differentiation	1/86	11/18866	0.049028425	0.215208675	0.174462702	SOX4	1
GO:0006751	Glutathione catabolic process	1/86	11/18866	0.049028425	0.215208675	0.174462702	CHAC1	1
GO:0006857	Oligopeptide transport	1/86	11/18866	0.049028425	0.215208675	0.174462702	SLC7A11	1
GO:0009950	Dorsal/ventral axis specification	1/86	11/18866	0.049028425	0.215208675	0.174462702	SMAD6	1
GO:0021561	Facial nerve development	1/86	11/18866	0.049028425	0.215208675	0.174462702	SEMA3A	1
GO:0021604	Cranial nerve structural organization	1/86	11/18866	0.049028425	0.215208675	0.174462702	SEMA3A	1
GO:0021610	Facial nerve morphogenesis	1/86	11/18866	0.049028425	0.215208675	0.174462702	SEMA3A	1
GO:0031442	Positive regulation of mRNA 3′-end processing	1/86	11/18866	0.049028425	0.215208675	0.174462702	CPEB3	1
GO:0032253	Dense core granule localization	1/86	11/18866	0.049028425	0.215208675	0.174462702	MAP2	1
GO:0032276	Regulation of gonadotropin secretion	1/86	11/18866	0.049028425	0.215208675	0.174462702	INHBB	1
GO:0032754	Positive regulation of interleukin-5 production	1/86	11/18866	0.049028425	0.215208675	0.174462702	GATA3	1
GO:0034776	Response to histamine	1/86	11/18866	0.049028425	0.215208675	0.174462702	GABRB3	1
GO:0035457	Cellular response to interferon-alpha	1/86	11/18866	0.049028425	0.215208675	0.174462702	GATA3	1
GO:0043455	Regulation of secondary metabolic process	1/86	11/18866	0.049028425	0.215208675	0.174462702	SLC7A11	1
GO:0043589	Skin morphogenesis	1/86	11/18866	0.049028425	0.215208675	0.174462702	TP63	1
GO:0044848	Biological phase	1/86	11/18866	0.049028425	0.215208675	0.174462702	TGFB2	1
GO:0046643	Regulation of gamma-delta T cell activation	1/86	11/18866	0.049028425	0.215208675	0.174462702	SOX4	1
GO:0048021	Regulation of melanin biosynthetic process	1/86	11/18866	0.049028425	0.215208675	0.174462702	SLC7A11	1
GO:0048102	Autophagic cell death	1/86	11/18866	0.049028425	0.215208675	0.174462702	TP53INP1	1
GO:0048103	Somatic stem cell division	1/86	11/18866	0.049028425	0.215208675	0.174462702	TGFB2	1
GO:0048672	Positive regulation of collateral sprouting	1/86	11/18866	0.049028425	0.215208675	0.174462702	BDNF	1
GO:0048742	Regulation of skeletal muscle fiber development	1/86	11/18866	0.049028425	0.215208675	0.174462702	HDAC9	1
GO:0051610	Serotonin uptake	1/86	11/18866	0.049028425	0.215208675	0.174462702	ITGB3	1
GO:0060174	Limb bud formation	1/86	11/18866	0.049028425	0.215208675	0.174462702	SOX4	1
GO:0060525	Prostate glandular acinus development	1/86	11/18866	0.049028425	0.215208675	0.174462702	TP63	1
GO:0061085	Regulation of histone H3-K27 methylation	1/86	11/18866	0.049028425	0.215208675	0.174462702	GATA3	1
GO:0061299	Retina vasculature morphogenesis in camera-type eye	1/86	11/18866	0.049028425	0.215208675	0.174462702	CLIC4	1
GO:0070254	Mucus secretion	1/86	11/18866	0.049028425	0.215208675	0.174462702	SYTL2	1
GO:0070933	Histone H4 deacetylation	1/86	11/18866	0.049028425	0.215208675	0.174462702	HDAC9	1
GO:0071281	Cellular response to iron ion	1/86	11/18866	0.049028425	0.215208675	0.174462702	ATP7A	1
GO:0090084	Negative regulation of inclusion body assembly	1/86	11/18866	0.049028425	0.215208675	0.174462702	SORL1	1
GO:0090309	Positive regulation of DNA methylation-dependent heterochromatin assembly	1/86	11/18866	0.049028425	0.215208675	0.174462702	ATF7IP	1
GO:0099519	Dense core granule cytoskeletal transport	1/86	11/18866	0.049028425	0.215208675	0.174462702	MAP2	1
GO:1900247	Regulation of cytoplasmic translational elongation	1/86	11/18866	0.049028425	0.215208675	0.174462702	CPEB3	1
GO:1900376	Regulation of secondary metabolite biosynthetic process	1/86	11/18866	0.049028425	0.215208675	0.174462702	SLC7A11	1
GO:1901950	Dense core granule transport	1/86	11/18866	0.049028425	0.215208675	0.174462702	MAP2	1
GO:1902513	Regulation of organelle transport along microtubule	1/86	11/18866	0.049028425	0.215208675	0.174462702	MAP2	1
GO:1904321	Response to forskolin	1/86	11/18866	0.049028425	0.215208675	0.174462702	AHR	1
GO:1904322	Cellular response to forskolin	1/86	11/18866	0.049028425	0.215208675	0.174462702	AHR	1
GO:1905245	Regulation of aspartic-type peptidase activity	1/86	11/18866	0.049028425	0.215208675	0.174462702	SORL1	1
GO:2000551	Regulation of T-helper 2 cell cytokine production	1/86	11/18866	0.049028425	0.215208675	0.174462702	GATA3	1
GO:2000574	Regulation of microtubule motor activity	1/86	11/18866	0.049028425	0.215208675	0.174462702	MAP2	1
GO:2000615	Regulation of histone H3-K9 acetylation	1/86	11/18866	0.049028425	0.215208675	0.174462702	GATA3	1
GO:0043367	CD4-positive, alpha-beta T cell differentiation	2/86	78/18866	0.049346708	0.215208675	0.174462702	GATA3/ATP7A	2
GO:0043900	Regulation of multi-organism process	2/86	78/18866	0.049346708	0.215208675	0.174462702	INHBB/PLCB1	2
GO:0060998	Regulation of dendritic spine development	2/86	78/18866	0.049346708	0.215208675	0.174462702	CPEB3/PPP1R9A	2
GO:0072332	Intrinsic apoptotic signaling pathway by p53 class mediator	2/86	78/18866	0.049346708	0.215208675	0.174462702	JMY/TP63	2
GO:1903522	Regulation of blood circulation	4/86	303/18866	0.049775935	0.215208675	0.174462702	TGFB2/SEMA3A/ANK2/BMPR2	4
GO:0030323	Respiratory tube development	3/86	181/18866	0.049849498	0.215208675	0.174462702	SLC7A11/ATP7A/BMPR2	3

Table S2.

Functional enrichment analysis (MF) of genes associated with the downregulated genes

ID	Description	GeneRatio	BgRatio	p-value	p.adjust	q-value	geneID	Count
GO:0031994	Insulin-like growth factor I binding	2/87	13/18352	0.001675018	0.273507638	0.253388116	ITGAV/ITGB3	2
GO:0003712	Transcription coregulator activity	8/87	498/18352	0.002489608	0.273507638	0.253388116	GATA3/NCOA2/RSF1/SOX4/HDAC9/ATF7IP/JMY/JMJD1C	8
GO:0017134	Fibroblast growth factor binding	2/87	23/18352	0.005268487	0.273507638	0.253388116	ITGAV/ITGB3	2
GO:0005160	Transforming growth factor beta receptor binding	2/87	24/18352	0.005729821	0.273507638	0.253388116	SMAD6/TGFB2	2
GO:0005546	Phosphatidylinositol-4,5-bisphosphate binding	3/87	82/18352	0.006959505	0.273507638	0.253388116	SYTL2/SESTD1/PLCB1	3
GO:0001968	Fibronectin binding	2/87	27/18352	0.007220079	0.273507638	0.253388116	ITGAV/ITGB3	2
GO:0005520	Insulin-like growth factor binding	2/87	29/18352	0.008300389	0.273507638	0.253388116	ITGAV/ITGB3	2
GO:0005126	Cytokine receptor binding	5/87	271/18352	0.009355786	0.273507638	0.253388116	GATA3/SMAD6/TGFB2/BDNF/ITGB3	5
GO:0019956	Chemokine binding	2/87	33/18352	0.010663192	0.273507638	0.253388116	ITGAV/ITGB3	2
GO:0015175	Neutral amino acid transmembrane transporter activity	2/87	34/18352	0.011295035	0.273507638	0.253388116	SLC7A11/SLC38A2	2
GO:0008022	Protein C-terminus binding	4/87	189/18352	0.012493832	0.273507638	0.253388116	PPP1R9A/MAGI1/SASH1/ATXN1	4
GO:0051015	Actin filament binding	4/87	206/18352	0.016646672	0.273507638	0.253388116	PPP1R9A/NEBL/MYO18A/CLMN	4
GO:1902936	Phosphatidylinositol bisphosphate binding	3/87	119/18352	0.018993105	0.273507638	0.253388116	SYTL2/SESTD1/PLCB1	3
GO:0048156	Tau protein binding	2/87	45/18352	0.019274238	0.273507638	0.253388116	TTBK2/MAP2	2
GO:0015026	Coreceptor activity	2/87	48/18352	0.021761265	0.273507638	0.253388116	ITGAV/ITGB3	2
GO:0016538	Cyclin-dependent protein serine/threonine kinase regulator activity	2/87	50/18352	0.023489237	0.273507638	0.253388116	CCNT1/CCNG2	2
GO:0070888	E-box binding	2/87	50/18352	0.023489237	0.273507638	0.253388116	AHR/GATA3	2
GO:0022853	Active ion transmembrane transporter activity	4/87	229/18352	0.023508097	0.273507638	0.253388116	SLC7A11/SLC24A1/ATP7A/SLC38A2	4
GO:0019955	Cytokine binding	3/87	135/18352	0.026361093	0.273507638	0.253388116	ITGAV/BMPR2/ITGB3	3
GO:0019838	Growth factor binding	3/87	136/18352	0.026865607	0.273507638	0.253388116	ITGAV/BMPR2/ITGB3	3
GO:0008509	Anion transmembrane transporter activity	5/87	357/18352	0.027380166	0.273507638	0.253388116	SLC7A11/CLIC4/SLC24A1/GABRB3/SLC38A2	5
GO:0005080	Protein kinase C binding	2/87	55/18352	0.028045437	0.273507638	0.253388116	HDAC9/ITGAV	2
GO:0050840	Extracellular matrix binding	2/87	57/18352	0.029959408	0.273507638	0.253388116	ITGAV/ITGB3	2
GO:0015179	l-amino acid transmembrane transporter activity	2/87	59/18352	0.031923969	0.273507638	0.253388116	SLC7A11/SLC38A2	2
GO:0003713	Transcription coactivator activity	4/87	267/18352	0.038154759	0.273507638	0.253388116	GATA3/NCOA2/SOX4/JMY	4
GO:0002039	p53 binding	2/87	66/18352	0.039182529	0.273507638	0.253388116	NUAK1/TP63	2
GO:0008083	Growth factor activity	3/87	162/18352	0.041782078	0.273507638	0.253388116	TGFB2/BDNF/INHBB	3
GO:0072509	Divalent inorganic cation transmembrane transporter activity	3/87	162/18352	0.041782078	0.273507638	0.253388116	SLC24A1/ATP7A/ITGAV	3
GO:0001094	TFIID-class transcription factor complex binding	1/87	10/18352	0.046418788	0.273507638	0.253388116	AHR	1
GO:0002162	Dystroglycan binding	1/87	10/18352	0.046418788	0.273507638	0.253388116	MAP2	1
GO:0004690	Cyclic nucleotide-dependent protein kinase activity	1/87	10/18352	0.046418788	0.273507638	0.253388116	PRKG1	1
GO:0005432	Calcium:sodium antiporter activity	1/87	10/18352	0.046418788	0.273507638	0.253388116	SLC24A1	1
GO:0016868	Intramolecular transferase activity, phosphotransferases	1/87	10/18352	0.046418788	0.273507638	0.253388116	PGM2L1	1
GO:0017002	Activin-activated receptor activity	1/87	10/18352	0.046418788	0.273507638	0.253388116	BMPR2	1
GO:0030957	Tat protein binding	1/87	10/18352	0.046418788	0.273507638	0.253388116	GABARAPL1	1
GO:0031078	Histone deacetylase activity (H3-K14 specific)	1/87	10/18352	0.046418788	0.273507638	0.253388116	HDAC9	1
GO:0032041	NAD-dependent histone deacetylase activity (H3-K14 specific)	1/87	10/18352	0.046418788	0.273507638	0.253388116	HDAC9	1
GO:0140104	Molecular carrier activity	1/87	10/18352	0.046418788	0.273507638	0.253388116	ATP7A	1
GO:0001618	Virus receptor activity	2/87	74/18352	0.048161835	0.273507638	0.253388116	ITGAV/ITGB3	2
GO:0140272	Exogenous protein binding	2/87	74/18352	0.048161835	0.273507638	0.253388116	ITGAV/ITGB3	2
GO:0005254	Chloride channel activity	2/87	75/18352	0.049332465	0.273507638	0.253388116	CLIC4/GABRB3	2

Table S3.

Functional enrichment analysis (CC) of downregulated genes

ID	Description	GeneRatio	BgRatio	p-value	p.adjust	q-value	geneID	Count
GO:0043034	Costamere	3/89	19/19559	8.37177E-05	0.018250458	0.013835451	PGM5/ANK2/AHNAK2	3
GO:0042641	Actomyosin	4/89	79/19559	0.000463912	0.036256484	0.027485601	NEBL/PGM5/LPP/MYO18A	4
GO:0098858	Actin-based cell projection	6/89	220/19559	0.000505501	0.036256484	0.027485601	PPP1R9A/CLIC4/ATP7A/ITGAV/MAP2/ITGB3	6
GO:0031252	Cell leading edge	8/89	421/19559	0.000665257	0.036256484	0.027485601	PPP1R9A/ATP7A/ITGAV/GABARAPL1/PACSIN1/JMY/NEDD9/ITGB3	8
GO:0005902	Microvillus	4/89	93/19559	0.000858959	0.037450592	0.02839084	CLIC4/ATP7A/ITGAV/ITGB3	4
GO:0044214	Spanning component of plasma membrane	2/89	12/19559	0.001311795	0.043519068	0.032991278	SLC24A1/BMPR2	2
GO:0030175	Filopodium	4/89	106/19559	0.001397401	0.043519068	0.032991278	PPP1R9A/ITGAV/MAP2/ITGB3	4
GO:0030014	CCR4-NOT complex	2/89	16/19559	0.002357022	0.052272891	0.039627445	CPEB3/CNOT6L	2
GO:0030018	Z disc	4/89	128/19559	0.002782162	0.052272891	0.039627445	NEBL/PGM5/ANK2/AHNAK2	4
GO:0031527	Filopodium membrane	2/89	18/19559	0.002987491	0.052272891	0.039627445	ITGAV/ITGB3	2
GO:0097440	Apical dendrite	2/89	18/19559	0.002987491	0.052272891	0.039627445	CPEB3/MAP2	2
GO:0089717	Spanning component of membrane	2/89	19/19559	0.003329111	0.052272891	0.039627445	SLC24A1/BMPR2	2
GO:0042383	Sarcolemma	4/89	135/19559	0.003369092	0.052272891	0.039627445	PGM5/ANK2/SLC38A2/AHNAK2	4
GO:0001725	Stress fiber	3/89	68/19559	0.003687104	0.052272891	0.039627445	NEBL/PGM5/LPP	3
GO:0097517	Contractile actin filament bundle	3/89	68/19559	0.003687104	0.052272891	0.039627445	NEBL/PGM5/LPP	3
GO:0031674	I band	4/89	140/19559	0.003836542	0.052272891	0.039627445	NEBL/PGM5/ANK2/AHNAK2	4
GO:0031258	Lamellipodium membrane	2/89	22/19559	0.004457567	0.057161747	0.043333628	ITGAV/ITGB3	2
GO:0031253	Cell projection membrane	6/89	344/19559	0.004845054	0.057814402	0.043828397	SLC7A11/ATP7A/ITGAV/GABARAPL1/PACSIN1/ITGB3	6
GO:0032432	Actin filament bundle	3/89	76/19559	0.00503887	0.057814402	0.043828397	NEBL/PGM5/LPP	3
GO:0031528	Microvillus membrane	2/89	26/19559	0.006197936	0.067557503	0.051214524	ITGAV/ITGB3	2
GO:0005911	Cell-cell junction	7/89	493/19559	0.007222799	0.074979535	0.056841077	MAGI1/CGNL1/CLIC4/PGM5/ANK2/BMPR2/ITGB3	7
GO:0031256	Leading edge membrane	4/89	175/19559	0.008381702	0.082823288	0.062787331	ITGAV/GABARAPL1/PACSIN1/ITGB3	4
GO:0008305	Integrin complex	2/89	31/19559	0.008738237	0.082823288	0.062787331	ITGAV/ITGB3	2
GO:0032587	Ruffle membrane	3/89	95/19559	0.009326562	0.08471627	0.064222378	ITGAV/PACSIN1/ITGB3	3
GO:0032839	Dendrite cytoplasm	2/89	34/19559	0.010449687	0.091121271	0.069077931	GABARAPL1/MAP2	2
GO:0098636	Protein complex involved in cell adhesion	2/89	36/19559	0.011666204	0.097816632	0.074153603	ITGAV/ITGB3	2
GO:0005903	Brush border	3/89	106/19559	0.012543653	0.10127838	0.076777912	SLC7A11/ATP7A/SLC38A2	3
GO:0030027	Lamellipodium	4/89	201/19559	0.013409681	0.104403946	0.079147366	PPP1R9A/ITGAV/NEDD9/ITGB3	4
GO:0030017	Sarcomere	4/89	207/19559	0.014792138	0.111196071	0.084296394	NEBL/PGM5/ANK2/AHNAK2	4
GO:0000307	Cyclin-dependent protein kinase holoenzyme complex	2/89	43/19559	0.016381768	0.119040851	0.090243426	CCNT1/CCNG2	2
GO:0030016	Myofibril	4/89	227/19559	0.020039059	0.140919836	0.106829619	NEBL/PGM5/ANK2/AHNAK2	4
GO:0034707	Chloride channel complex	2/89	50/19559	0.021772834	0.144876464	0.109829091	CLIC4/GABRB3	2
GO:0034399	Nuclear periphery	3/89	131/19559	0.021959481	0.144876464	0.109829091	CLIC4/ATXN1/MAP2	3
GO:0014704	Intercalated disc	2/89	51/19559	0.022595412	0.144876464	0.109829091	PGM5/ANK2	2
GO:0043292	Contractile fiber	4/89	238/19559	0.023357656	0.145484828	0.110290285	NEBL/PGM5/ANK2/AHNAK2	4
GO:0098978	Glutamatergic synapse	5/89	361/19559	0.024523154	0.147057064	0.111482178	PPP1R9A/FBXL20/BCAN/PLCB1/ITGB3	5
GO:0030315	T-tubule	2/89	54/19559	0.025138884	0.147057064	0.111482178	ANK2/AHNAK2	2
GO:0005802	Trans-Golgi network	4/89	245/19559	0.0256338	0.147057064	0.111482178	SORL1/ATP7A/MYO18A/CHAC1	4
GO:0016459	Myosin complex	2/89	57/19559	0.027793265	0.155357222	0.117774427	CGNL1/MYO18A	2
GO:0031526	Brush border membrane	2/89	58/19559	0.028702113	0.156426515	0.118585046	SLC7A11/ATP7A	2
GO:0036064	Ciliary basal body	3/89	155/19559	0.033795659	0.175834844	0.133298264	RABL2B/TTBK2/LCA5	3
GO:0098862	Cluster of actin-based cell projections	3/89	159/19559	0.036033328	0.175834844	0.133298264	SLC7A11/ATP7A/SLC38A2	3
GO:0035869	Ciliary transition zone	2/89	68/19559	0.038420498	0.175834844	0.133298264	TTBK2/LCA5	2
GO:0005912	Adherens junction	3/89	166/19559	0.040128844	0.175834844	0.133298264	MAGI1/PGM5/BMPR2	3
GO:0005667	Transcription regulator complex	5/89	413/19559	0.040249424	0.175834844	0.133298264	AHR/SKIL/SMAD6/HDAC9/ATF7IP	5
GO:0005925	Focal adhesion	5/89	415/19559	0.040953218	0.175834844	0.133298264	PGM5/LPP/ITGAV/NEDD9/ITGB3	5
GO:0030055	Cell-substrate junction	5/89	423/19559	0.043843336	0.175834844	0.133298264	PGM5/LPP/ITGAV/NEDD9/ITGB3	5
GO:0005641	Nuclear envelope lumen	1/89	10/19559	0.044592867	0.175834844	0.133298264	SORL1	1
GO:1990124	Messenger ribonucleoprotein complex	1/89	10/19559	0.044592867	0.175834844	0.133298264	CPEB3	1
GO:0044291	Cell-cell contact zone	2/89	74/19559	0.044768917	0.175834844	0.133298264	PGM5/ANK2	2
GO:0098982	GABA-ergic synapse	2/89	74/19559	0.044768917	0.175834844	0.133298264	GABRB3/PLCB1	2
GO:0045177	Apical part of cell	5/89	433/19559	0.047625364	0.175834844	0.133298264	SLC7A11/CLIC4/ATP7A/ANK2/BMPR2	5
GO:0000118	Histone deacetylase complex	2/89	77/19559	0.048078825	0.175834844	0.133298264	HDAC9/JMJD1C	2
GO:0001726	Ruffle	3/89	179/19559	0.048332303	0.175834844	0.133298264	ITGAV/PACSIN1/ITGB3	3
GO:0031010	ISWI-type complex	1/89	11/19559	0.048942513	0.175834844	0.133298264	RSF1	1
GO:0034992	Microtubule organizing center attachment site	1/89	11/19559	0.048942513	0.175834844	0.133298264	CLMN	1
GO:0034993	Meiotic nuclear membrane microtubule tethering complex	1/89	11/19559	0.048942513	0.175834844	0.133298264	CLMN	1
GO:0097470	Ribbon synapse	1/89	11/19559	0.048942513	0.175834844	0.133298264	PACSIN1	1
GO:0106083	Nuclear membrane protein complex	1/89	11/19559	0.048942513	0.175834844	0.133298264	CLMN	1
GO:0106094	Nuclear membrane microtubule tethering complex	1/89	11/19559	0.048942513	0.175834844	0.133298264	CLMN	1
GO:0016234	Inclusion body	2/89	78/19559	0.049201493	0.175834844	0.133298264	ATXN1/KLF8	2

Table S4.

Functional enrichment analysis (KEGG) of genes associated with the downregulated genes

ID	Description	GeneRatio	BgRatio	p-value	p.adjust	q-value	geneID	Count
hsa04350	TGF-beta signaling pathway	5/45	96/8223	0.00016491	0.022922444	0.02187223	FST/SMAD6/TGFB2/INHBB/BMPR2	5
hsa04919	Thyroid hormone signaling pathway	4/45	121/8223	0.004173019	0.290024833	0.276737062	NCOA2/ITGAV/PLCB1/ITGB3	4
hsa04727	GABAergic synapse	3/45	89/8223	0.012533392	0.426926226	0.407366183	GABRB3/SLC38A2/GABARAPL1	3
hsa05410	Hypertrophic cardiomyopathy	3/45	90/8223	0.012916633	0.426926226	0.407366183	TGFB2/ITGAV/ITGB3	3
hsa05414	Dilated cardiomyopathy	3/45	96/8223	0.015357058	0.426926226	0.407366183	TGFB2/ITGAV/ITGB3	3
hsa05205	Proteoglycans in cancer	4/45	205/8223	0.025196801	0.497873197	0.475062649	TGFB2/ANK2/ITGAV/ITGB3	4
hsa05206	MicroRNAs in cancer	5/45	310/8223	0.026240318	0.497873197	0.475062649	TGFB2/SOX4/BMPR2/ITGB3/TP63	5
hsa04611	Platelet activation	3/45	124/8223	0.029996051	0.497873197	0.475062649	PLCB1/PRKG1/ITGB3	3
hsa04068	FoxO signaling pathway	3/45	131/8223	0.034496116	0.497873197	0.475062649	TGFB2/CCNG2/GABARAPL1	3
hsa05418	Fluid shear stress and atherosclerosis	3/45	139/8223	0.040045963	0.497873197	0.475062649	ITGAV/BMPR2/ITGB3	3
hsa04730	Long-term depression	2/45	60/8223	0.04241652	0.497873197	0.475062649	PLCB1/PRKG1	2
hsa04550	Signaling pathways regulating pluripotency of stem cells	3/45	143/8223	0.042981859	0.497873197	0.475062649	SKIL/INHBB/BMPR2	3
hsa05321	Inflammatory bowel disease	2/45	65/8223	0.049000918	0.523932893	0.499928395	GATA3/TGFB2	2

Table S5.

Functional enrichment analysis (BP) of the DEGs associated with the upregulated genes

ID	Description	GeneRatio	BgRatio	p-value	p.adjust	q-value	geneID	Count
GO:0048660	Regulation of smooth muscle cell proliferation	5/38	173/18866	2.40386E-05	0.014098915	0.011725698	TNFAIP3/APLN/IGFBP3/MYB/S1PR1	5
GO:0048659	Smooth muscle cell proliferation	5/38	175/18866	2.54034E-05	0.014098915	0.011725698	TNFAIP3/APLN/IGFBP3/MYB/S1PR1	5
GO:0071222	Cellular response to lipopolysaccharide	5/38	208/18866	5.79563E-05	0.020270505	0.016858447	CXCL3/PPBP/TNFAIP3/CXCL2/SERPINE1	5
GO:0071219	Cellular response to molecule of bacterial origin	5/38	222/18866	7.88877E-05	0.020270505	0.016858447	CXCL3/PPBP/TNFAIP3/CXCL2/SERPINE1	5
GO:0030595	Leukocyte chemotaxis	5/38	232/18866	9.70957E-05	0.020270505	0.016858447	CXCL3/PPBP/CXCL2/S1PR1/SERPINE1	5
GO:0033002	Muscle cell proliferation	5/38	244/18866	0.000123037	0.020270505	0.016858447	TNFAIP3/APLN/IGFBP3/MYB/S1PR1	5
GO:0071216	Cellular response to biotic stimulus	5/38	246/18866	0.000127832	0.020270505	0.016858447	CXCL3/PPBP/TNFAIP3/CXCL2/SERPINE1	5
GO:0070424	Regulation of nucleotide-binding oligomerization domain containing signaling pathway	2/38	10/18866	0.000175971	0.024415911	0.020306073	TNFAIP3/HSPA1B	2
GO:0061043	Regulation of vascular wound healing	2/38	13/18866	0.000303854	0.0350297	0.029133283	TNFAIP3/SERPINE1	2
GO:0070431	Nucleotide-binding oligomerization domain containing 2 signaling pathway	2/38	14/18866	0.000354046	0.0350297	0.029133283	TNFAIP3/HSPA1B	2
GO:0048662	Negative regulation of smooth muscle cell proliferation	3/38	69/18866	0.000360371	0.0350297	0.029133283	TNFAIP3/APLN/IGFBP3	3
GO:0060326	Cell chemotaxis	5/38	311/18866	0.000378699	0.0350297	0.029133283	CXCL3/PPBP/CXCL2/S1PR1/SERPINE1	5
GO:0061844	Antimicrobial humoral immune response mediated by antimicrobial peptide	3/38	75/18866	0.000460592	0.039327508	0.032707657	CXCL3/PPBP/CXCL2	3
GO:0032496	Response to lipopolysaccharide	5/38	334/18866	0.000524346	0.041184338	0.034251934	CXCL3/PPBP/TNFAIP3/CXCL2/SERPINE1	5
GO:0031397	Negative regulation of protein ubiquitination	3/38	80/18866	0.000556545	0.041184338	0.034251934	TNFAIP3/DNAJA1/HSPA1B	3
GO:0002237	Response to molecule of bacterial origin	5/38	356/18866	0.000699847	0.048000435	0.039920704	CXCL3/PPBP/TNFAIP3/CXCL2/SERPINE1	5
GO:0070098	Chemokine-mediated signaling pathway	3/38	88/18866	0.000735142	0.048000435	0.039920704	CXCL3/PPBP/CXCL2	3
GO:0061042	Vascular wound healing	2/38	21/18866	0.000809794	0.048876902	0.040649638	TNFAIP3/SERPINE1	2
GO:1903321	Negative regulation of protein modification by small protein conjugation or removal	3/38	92/18866	0.000836632	0.048876902	0.040649638	TNFAIP3/DNAJA1/HSPA1B	3
GO:1990868	Response to chemokine	3/38	97/18866	0.000975483	0.050782909	0.042234813	CXCL3/PPBP/CXCL2	3
GO:1990869	Cellular response to chemokine	3/38	97/18866	0.000975483	0.050782909	0.042234813	CXCL3/PPBP/CXCL2	3
GO:0097529	Myeloid leukocyte migration	4/38	222/18866	0.001006508	0.050782909	0.042234813	CXCL3/PPBP/CXCL2/SERPINE1	4
GO:0000079	Regulation of cyclin-dependent protein serine/threonine kinase activity	3/38	102/18866	0.001128148	0.053244499	0.044282054	TNFAIP3/CDC25A/CDKN3	3
GO:0030593	Neutrophil chemotaxis	3/38	103/18866	0.001160384	0.053244499	0.044282054	CXCL3/PPBP/CXCL2	3
GO:2001234	Negative regulation of apoptotic signaling pathway	4/38	233/18866	0.001203717	0.053244499	0.044282054	TNFAIP3/DNAJA1/SERPINE1/HSPA1B	4
GO:1904029	Regulation of cyclin-dependent protein kinase activity	3/38	106/18866	0.001260569	0.053244499	0.044282054	TNFAIP3/CDC25A/CDKN3	3
GO:2001237	Negative regulation of extrinsic apoptotic signaling pathway	3/38	107/18866	0.001295136	0.053244499	0.044282054	TNFAIP3/SERPINE1/HSPA1B	3
GO:0060055	Angiogenesis involved in wound healing	2/38	30/18866	0.001658373	0.065742634	0.054676425	TNFAIP3/SERPINE1	2
GO:1990266	Neutrophil migration	3/38	122/18866	0.001886881	0.072222009	0.060065151	CXCL3/PPBP/CXCL2	3
GO:0071621	Granulocyte chemotaxis	3/38	127/18866	0.002115914	0.076192697	0.063367468	CXCL3/PPBP/CXCL2	3
GO:2000352	Negative regulation of endothelial cell apoptotic process	2/38	34/18866	0.002127904	0.076192697	0.063367468	TNFAIP3/SERPINE1	2
GO:0070423	Nucleotide-binding oligomerization domain containing signaling pathway	2/38	37/18866	0.002516584	0.084138903	0.069976119	TNFAIP3/HSPA1B	2
GO:0019730	Antimicrobial humoral response	3/38	137/18866	0.002624222	0.084138903	0.069976119	CXCL3/PPBP/CXCL2	3
GO:0014912	Negative regulation of smooth muscle cell migration	2/38	38/18866	0.002653028	0.084138903	0.069976119	IGFBP3/SERPINE1	2
GO:0035872	Nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway	2/38	38/18866	0.002653028	0.084138903	0.069976119	TNFAIP3/HSPA1B	2
GO:1902042	Negative regulation of extrinsic apoptotic signaling pathway via death domain receptors	2/38	41/18866	0.003082827	0.095053839	0.079053785	TNFAIP3/SERPINE1	2
GO:0071901	Negative regulation of protein serine/threonine kinase activity	3/38	148/18866	0.003263895	0.096472101	0.080233317	CHORDC1/TNFAIP3/DNAJA1	3
GO:0045124	Regulation of bone resorption	2/38	43/18866	0.003386278	0.096472101	0.080233317	TNFAIP3/S1PR1	2
GO:0097530	Granulocyte migration	3/38	150/18866	0.00338956	0.096472101	0.080233317	CXCL3/PPBP/CXCL2	3
GO:1904036	Negative regulation of epithelial cell apoptotic process	2/38	48/18866	0.004203334	0.113869229	0.094702052	TNFAIP3/SERPINE1	2
GO:2001236	Regulation of extrinsic apoptotic signaling pathway	3/38	162/18866	0.004205981	0.113869229	0.094702052	TNFAIP3/SERPINE1/HSPA1B	3
GO:0009408	Response to heat	3/38	166/18866	0.004502401	0.117537332	0.097752717	CHORDC1/DNAJA1/HSPA1B	3
GO:0046850	Regulation of bone remodeling	2/38	50/18866	0.004553248	0.117537332	0.097752717	TNFAIP3/S1PR1	2
GO:0060976	Coronary vasculature development	2/38	51/18866	0.004733101	0.119403217	0.099304525	ADAMTS6/APLN	2
GO:0048260	Positive regulation of receptor-mediated endocytosis	2/38	52/18866	0.004916199	0.121266244	0.100853955	APLN/SERPINE1	2
GO:0032757	Positive regulation of interleukin-8 production	2/38	54/18866	0.005292082	0.127700239	0.10620494	SERPINE1/HSPA1B	2
GO:0062197	Cellular response to chemical stress	4/38	360/18866	0.005769905	0.135973274	0.113085407	TNFAIP3/MYB/DNAJA1/HSPA1B	4
GO:0070936	Protein K48-linked ubiquitination	2/38	57/18866	0.005879925	0.135973274	0.113085407	TNFAIP3/UBE2D4	2
GO:0061077	Chaperone-mediated protein folding	2/38	60/18866	0.006496281	0.147160652	0.122389655	CHORDC1/HSPA1B	2
GO:1902041	Regulation of extrinsic apoptotic signaling pathway via death domain receptors	2/38	61/18866	0.006708009	0.147776298	0.122901673	TNFAIP3/SERPINE1	2
GO:0010803	Regulation of tumor necrosis factor-mediated signaling pathway	2/38	62/18866	0.006922854	0.147776298	0.122901673	TNFAIP3/HSPA1B	2
GO:2000351	Regulation of endothelial cell apoptotic process	2/38	62/18866	0.006922854	0.147776298	0.122901673	TNFAIP3/SERPINE1	2
GO:0045453	Bone resorption	2/38	64/18866	0.007361842	0.154181978	0.128229108	TNFAIP3/S1PR1	2
GO:0031331	Positive regulation of cellular catabolic process	4/38	390/18866	0.007622996	0.155713474	0.129502813	TNFAIP3/TOMM7/PIM2/HSPA1B	4
GO:0030198	Extracellular matrix organization	4/38	395/18866	0.007965878	0.155713474	0.129502813	ADAMTS6/ADAMTS14/SERPINE1/TGFBI	4
GO:0043062	Extracellular structure organization	4/38	396/18866	0.008035657	0.155713474	0.129502813	ADAMTS6/ADAMTS14/SERPINE1/TGFBI	4
GO:0002753	Cytoplasmic pattern recognition receptor signaling pathway	2/38	68/18866	0.008276662	0.155713474	0.129502813	TNFAIP3/HSPA1B	2
GO:0016239	Positive regulation of macroautophagy	2/38	68/18866	0.008276662	0.155713474	0.129502813	TOMM7/PIM2	2
GO:0072577	Endothelial cell apoptotic process	2/38	68/18866	0.008276662	0.155713474	0.129502813	TNFAIP3/SERPINE1	2
GO:0031396	Regulation of protein ubiquitination	3/38	211/18866	0.008724015	0.161394284	0.134227394	TNFAIP3/DNAJA1/HSPA1B	3
GO:0001503	Ossification	4/38	412/18866	0.009207614	0.166220297	0.138241063	CDH11/IGFBP3/STC1/S1PR1	4
GO:2001233	Regulation of apoptotic signaling pathway	4/38	413/18866	0.009284377	0.166220297	0.138241063	TNFAIP3/DNAJA1/SERPINE1/HSPA1B	4
GO:1903747	Regulation of establishment of protein localization to mitochondrion	2/38	73/18866	0.009488233	0.167173623	0.139033919	TOMM7/DNAJA1	2
GO:0006457	Protein folding	3/38	230/18866	0.011020819	0.185670592	0.154417363	CHORDC1/DNAJA1/HSPA1B	3
GO:0097191	Extrinsic apoptotic signaling pathway	3/38	230/18866	0.011020819	0.185670592	0.154417363	TNFAIP3/SERPINE1/HSPA1B	3
GO:1900034	Regulation of cellular response to heat	2/38	79/18866	0.011039873	0.185670592	0.154417363	CHORDC1/HSPA1B	2
GO:0009266	Response to temperature stimulus	3/38	233/18866	0.011412487	0.189072545	0.157246678	CHORDC1/DNAJA1/HSPA1B	3
GO:0001933	Negative regulation of protein phosphorylation	4/38	444/18866	0.011876361	0.193864123	0.161231708	CHORDC1/TNFAIP3/IGFBP3/DNAJA1	4
GO:0001819	Positive regulation of cytokine production	4/38	447/18866	0.012149539	0.195449108	0.162549898	POLR3G/MYB/SERPINE1/HSPA1B	4
GO:1903320	Regulation of protein modification by small protein conjugation or removal	3/38	242/18866	0.012635607	0.200132614	0.166445047	TNFAIP3/DNAJA1/HSPA1B	3
GO:0009896	Positive regulation of catabolic process	4/38	454/18866	0.01280268	0.200132614	0.166445047	TNFAIP3/TOMM7/PIM2/HSPA1B	4
GO:0014910	Regulation of smooth muscle cell migration	2/38	86/18866	0.012981575	0.200132614	0.166445047	IGFBP3/SERPINE1	2
GO:0006469	Negative regulation of protein kinase activity	3/38	246/18866	0.013202523	0.200750689	0.166959084	CHORDC1/TNFAIP3/DNAJA1	3
GO:0008625	Extrinsic apoptotic signaling pathway via death domain receptors	2/38	89/18866	0.013856109	0.205070406	0.17055168	TNFAIP3/SERPINE1	2
GO:0043506	Regulation of JUN kinase activity	2/38	89/18866	0.013856109	0.205070406	0.17055168	FZD8/DNAJA1	2
GO:0034103	Regulation of tissue remodeling	2/38	91/18866	0.014453019	0.208348715	0.173278163	TNFAIP3/S1PR1	2
GO:0046849	Bone remodeling	2/38	91/18866	0.014453019	0.208348715	0.173278163	TNFAIP3/S1PR1	2
GO:0014909	Smooth muscle cell migration	2/38	93/18866	0.01506093	0.211615603	0.175995148	IGFBP3/SERPINE1	2
GO:0032677	Regulation of interleukin-8 production	2/38	93/18866	0.01506093	0.211615603	0.175995148	SERPINE1/HSPA1B	2
GO:1904035	Regulation of epithelial cell apoptotic process	2/38	94/18866	0.015368982	0.213244626	0.177349964	TNFAIP3/SERPINE1	2
GO:0042326	Negative regulation of phosphorylation	4/38	484/18866	0.015856817	0.217297123	0.18072032	CHORDC1/TNFAIP3/IGFBP3/DNAJA1	4
GO:0033673	Negative regulation of kinase activity	3/38	268/18866	0.01657976	0.219402235	0.182471086	CHORDC1/TNFAIP3/DNAJA1	3
GO:0062207	Regulation of pattern recognition receptor signaling pathway	2/38	99/18866	0.016949739	0.219402235	0.182471086	TNFAIP3/HSPA1B	2
GO:0045807	Positive regulation of endocytosis	2/38	100/18866	0.017273909	0.219402235	0.182471086	APLN/SERPINE1	2
GO:0070301	Cellular response to hydrogen peroxide	2/38	100/18866	0.017273909	0.219402235	0.182471086	TNFAIP3/MYB	2
GO:0032637	Interleukin-8 production	2/38	101/18866	0.017600726	0.219402235	0.182471086	SERPINE1/HSPA1B	2
GO:1990542	Mitochondrial transmembrane transport	2/38	101/18866	0.017600726	0.219402235	0.182471086	SLC25A12/TOMM7	2
GO:0035335	Peptidyl-tyrosine dephosphorylation	2/38	103/18866	0.018262253	0.219402235	0.182471086	CDC25A/CDKN3	2
GO:0048661	Positive regulation of smooth muscle cell proliferation	2/38	103/18866	0.018262253	0.219402235	0.182471086	MYB/S1PR1	2
GO:0048259	Regulation of receptor-mediated endocytosis	2/38	105/18866	0.018934228	0.219402235	0.182471086	APLN/SERPINE1	2
GO:0014812	Muscle cell migration	2/38	106/18866	0.019274106	0.219402235	0.182471086	IGFBP3/SERPINE1	2
GO:0000082	G1/S transition of mitotic cell cycle	3/38	287/18866	0.019853233	0.219402235	0.182471086	CDC25A/CDKN3/PIM2	3
GO:0002676	Regulation of chronic inflammatory response	1/38	10/18866	0.019965185	0.219402235	0.182471086	TNFAIP3	1
GO:0003376	Sphingosine-1-phosphate receptor signaling pathway	1/38	10/18866	0.019965185	0.219402235	0.182471086	S1PR1	1
GO:0034135	Regulation of toll-like receptor 2 signaling pathway	1/38	10/18866	0.019965185	0.219402235	0.182471086	TNFAIP3	1
GO:0035871	Protein K11-linked deubiquitination	1/38	10/18866	0.019965185	0.219402235	0.182471086	TNFAIP3	1
GO:0042756	Drinking behavior	1/38	10/18866	0.019965185	0.219402235	0.182471086	APLN	1
GO:0051409	Response to nitrosative stress	1/38	10/18866	0.019965185	0.219402235	0.182471086	DNAJA1	1
GO:0051918	Negative regulation of fibrinolysis	1/38	10/18866	0.019965185	0.219402235	0.182471086	SERPINE1	1
GO:0098779	Positive regulation of mitophagy in response to mitochondrial depolarization	1/38	10/18866	0.019965185	0.219402235	0.182471086	TOMM7	1
GO:0031647	Regulation of protein stability	3/38	296/18866	0.021520184	0.219402235	0.182471086	TOMM7/PIM2/HSPA1B	3
GO:0051348	Negative regulation of transferase activity	3/38	296/18866	0.021520184	0.219402235	0.182471086	CHORDC1/TNFAIP3/DNAJA1	3
GO:0032963	Collagen metabolic process	2/38	113/18866	0.021724827	0.219402235	0.182471086	MYB/ADAMTS14	2
GO:0070268	Cornification	2/38	113/18866	0.021724827	0.219402235	0.182471086	KRT6B/KRT75	2
GO:0016078	tRNA catabolic process	1/38	11/18866	0.021940223	0.219402235	0.182471086	POP1	1
GO:0031652	Positive regulation of heat generation	1/38	11/18866	0.021940223	0.219402235	0.182471086	APLN	1
GO:0051574	Positive regulation of histone H3-K9 methylation	1/38	11/18866	0.021940223	0.219402235	0.182471086	MYB	1
GO:0070778	l-aspartate transmembrane transport	1/38	11/18866	0.021940223	0.219402235	0.182471086	SLC25A12	1
GO:0090084	Negative regulation of inclusion body assembly	1/38	11/18866	0.021940223	0.219402235	0.182471086	HSPA1B	1
GO:1901526	Positive regulation of mitophagy	1/38	11/18866	0.021940223	0.219402235	0.182471086	TOMM7	1
GO:1903265	Positive regulation of tumor necrosis factor-mediated signaling pathway	1/38	11/18866	0.021940223	0.219402235	0.182471086	HSPA1B	1
GO:0031109	Microtubule polymerization or depolymerization	2/38	117/18866	0.023180502	0.220532534	0.183411126	KIF18B/HSPA1B	2
GO:0045446	Endothelial cell differentiation	2/38	117/18866	0.023180502	0.220532534	0.183411126	STC1/S1PR1	2
GO:1904019	Epithelial cell apoptotic process	2/38	117/18866	0.023180502	0.220532534	0.183411126	TNFAIP3/SERPINE1	2
GO:0010755	Regulation of plasminogen activation	1/38	12/18866	0.023911386	0.220532534	0.183411126	SERPINE1	1
GO:0033629	Negative regulation of cell adhesion mediated by integrin	1/38	12/18866	0.023911386	0.220532534	0.183411126	SERPINE1	1
GO:0060536	Cartilage morphogenesis	1/38	12/18866	0.023911386	0.220532534	0.183411126	STC1	1
GO:0072537	Fibroblast activation	1/38	12/18866	0.023911386	0.220532534	0.183411126	MYB	1
GO:0090520	Sphingolipid mediated signaling pathway	1/38	12/18866	0.023911386	0.220532534	0.183411126	S1PR1	1
GO:0034599	Cellular response to oxidative stress	3/38	310/18866	0.024262434	0.220532534	0.183411126	TNFAIP3/MYB/HSPA1B	3
GO:0044843	Cell cycle G1/S phase transition	3/38	310/18866	0.024262434	0.220532534	0.183411126	CDC25A/CDKN3/PIM2	3
GO:0010906	Regulation of glucose metabolic process	2/38	121/18866	0.024675494	0.220532534	0.183411126	IGFBP3/SLC25A12	2
GO:0001682	tRNA 5′-leader removal	1/38	13/18866	0.02587868	0.220532534	0.183411126	POP1	1
GO:0006596	Polyamine biosynthetic process	1/38	13/18866	0.02587868	0.220532534	0.183411126	SRM	1
GO:0031650	Regulation of heat generation	1/38	13/18866	0.02587868	0.220532534	0.183411126	APLN	1
GO:0031665	Negative regulation of lipopolysaccharide-mediated signaling pathway	1/38	13/18866	0.02587868	0.220532534	0.183411126	TNFAIP3	1
GO:0034144	Negative regulation of toll-like receptor 4 signaling pathway	1/38	13/18866	0.02587868	0.220532534	0.183411126	TNFAIP3	1
GO:0043568	Positive regulation of insulin-like growth factor receptor signaling pathway	1/38	13/18866	0.02587868	0.220532534	0.183411126	IGFBP3	1
GO:0032479	Regulation of type I interferon production	2/38	125/18866	0.026209113	0.220532534	0.183411126	POLR3G/TNFAIP3	2
GO:0034605	Cellular response to heat	2/38	125/18866	0.026209113	0.220532534	0.183411126	CHORDC1/HSPA1B	2
GO:0006470	Protein dephosphorylation	3/38	323/18866	0.026971601	0.220532534	0.183411126	IGFBP3/CDC25A/CDKN3	3
GO:0032606	Type I interferon production	2/38	127/18866	0.026990194	0.220532534	0.183411126	POLR3G/TNFAIP3	2
GO:0002576	Platelet degranulation	2/38	129/18866	0.027780676	0.220532534	0.183411126	PPBP/SERPINE1	2
GO:0001886	Endothelial cell morphogenesis	1/38	14/18866	0.027842114	0.220532534	0.183411126	STC1	1
GO:0043650	Dicarboxylic acid biosynthetic process	1/38	14/18866	0.027842114	0.220532534	0.183411126	SLC25A12	1
GO:0051917	Regulation of fibrinolysis	1/38	14/18866	0.027842114	0.220532534	0.183411126	SERPINE1	1
GO:0090399	Replicative senescence	1/38	14/18866	0.027842114	0.220532534	0.183411126	SERPINE1	1
GO:1904925	Positive regulation of autophagy of mitochondrion in response to mitochondrial depolarization	1/38	14/18866	0.027842114	0.220532534	0.183411126	TOMM7	1
GO:0010508	Positive regulation of autophagy	2/38	131/18866	0.028580476	0.220532534	0.183411126	TOMM7/PIM2	2
GO:0046887	Positive regulation of hormone secretion	2/38	131/18866	0.028580476	0.220532534	0.183411126	APLN/MYB	2
GO:0002467	Germinal center formation	1/38	15/18866	0.029801694	0.220532534	0.183411126	TNFAIP3	1
GO:0006089	Lactate metabolic process	1/38	15/18866	0.029801694	0.220532534	0.183411126	SLC25A12	1
GO:0007638	Mechanosensory behavior	1/38	15/18866	0.029801694	0.220532534	0.183411126	STRBP	1
GO:0016114	Terpenoid biosynthetic process	1/38	15/18866	0.029801694	0.220532534	0.183411126	DHRS9	1
GO:0023035	CD40 signaling pathway	1/38	15/18866	0.029801694	0.220532534	0.183411126	TNFAIP3	1
GO:0034134	Toll-like receptor 2 signaling pathway	1/38	15/18866	0.029801694	0.220532534	0.183411126	TNFAIP3	1
GO:0045779	Negative regulation of bone resorption	1/38	15/18866	0.029801694	0.220532534	0.183411126	TNFAIP3	1
GO:1904923	Regulation of autophagy of mitochondrion in response to mitochondrial depolarization	1/38	15/18866	0.029801694	0.220532534	0.183411126	TOMM7	1
GO:2000345	Regulation of hepatocyte proliferation	1/38	15/18866	0.029801694	0.220532534	0.183411126	TNFAIP3	1
GO:2001171	Positive regulation of ATP biosynthetic process	1/38	15/18866	0.029801694	0.220532534	0.183411126	SLC25A12	1
GO:0003158	Endothelium development	2/38	135/18866	0.030207696	0.220595672	0.183463636	STC1/S1PR1	2
GO:0015748	Organophosphate ester transport	2/38	135/18866	0.030207696	0.220595672	0.183463636	SLC25A12/PITPNM2	2
GO:0006595	Polyamine metabolic process	1/38	16/18866	0.031757427	0.224527035	0.186733247	SRM	1
GO:0043508	Negative regulation of JUN kinase activity	1/38	16/18866	0.031757427	0.224527035	0.186733247	DNAJA1	1
GO:0048012	Hepatocyte growth factor receptor signaling pathway	1/38	16/18866	0.031757427	0.224527035	0.186733247	ESM1	1
GO:0090083	Regulation of inclusion body assembly	1/38	16/18866	0.031757427	0.224527035	0.186733247	HSPA1B	1
GO:0099116	tRNA 5′-end processing	1/38	16/18866	0.031757427	0.224527035	0.186733247	POP1	1
GO:0072655	Establishment of protein localization to mitochondrion	2/38	140/18866	0.032292653	0.224646621	0.186832704	TOMM7/DNAJA1	2
GO:0009615	Response to virus	3/38	349/18866	0.032859219	0.224646621	0.186832704	POLR3G/TNFAIP3/PIM2	3
GO:0030336	Negative regulation of cell migration	3/38	350/18866	0.033098116	0.224646621	0.186832704	IGFBP3/STC1/SERPINE1	3
GO:0002031	G protein-coupled receptor internalization	1/38	17/18866	0.033709322	0.224646621	0.186832704	APLN	1
GO:0009084	Glutamine family amino acid biosynthetic process	1/38	17/18866	0.033709322	0.224646621	0.186832704	SLC25A12	1
GO:0031649	Heat generation	1/38	17/18866	0.033709322	0.224646621	0.186832704	APLN	1
GO:0042448	Progesterone metabolic process	1/38	17/18866	0.033709322	0.224646621	0.186832704	DHRS9	1
GO:0046851	Negative regulation of bone remodeling	1/38	17/18866	0.033709322	0.224646621	0.186832704	TNFAIP3	1
GO:1901673	Regulation of mitotic spindle assembly	1/38	17/18866	0.033709322	0.224646621	0.186832704	HSPA1B	1
GO:0050921	Positive regulation of chemotaxis	2/38	144/18866	0.03400057	0.224646621	0.186832704	S1PR1/SERPINE1	2
GO:0070585	Protein localization to mitochondrion	2/38	144/18866	0.03400057	0.224646621	0.186832704	TOMM7/DNAJA1	2
GO:0042542	Response to hydrogen peroxide	2/38	146/18866	0.034867623	0.229012195	0.190463438	TNFAIP3/MYB	2
GO:0007043	Cell-cell junction assembly	2/38	147/18866	0.035304388	0.22932859	0.190726575	CDH11/TLN2	2
GO:0051571	Positive regulation of histone H3-K4 methylation	1/38	18/18866	0.035657386	0.22932859	0.190726575	MYB	1
GO:1901524	Regulation of mitophagy	1/38	18/18866	0.035657386	0.22932859	0.190726575	TOMM7	1
GO:0010675	Regulation of cellular carbohydrate metabolic process	2/38	148/18866	0.035743298	0.22932859	0.190726575	IGFBP3/SLC25A12	2
GO:1903364	Positive regulation of cellular protein catabolic process	2/38	149/18866	0.036184345	0.22932859	0.190726575	TNFAIP3/HSPA1B	2
GO:2000146	Negative regulation of cell motility	3/38	365/18866	0.036791555	0.22932859	0.190726575	IGFBP3/STC1/SERPINE1	3
GO:0061041	Regulation of wound healing	2/38	151/18866	0.037072807	0.22932859	0.190726575	TNFAIP3/SERPINE1	2
GO:0003417	Growth plate cartilage development	1/38	19/18866	0.037601625	0.22932859	0.190726575	STC1	1
GO:0030150	Protein import into mitochondrial matrix	1/38	19/18866	0.037601625	0.22932859	0.190726575	TOMM7	1
GO:0031643	Positive regulation of myelination	1/38	19/18866	0.037601625	0.22932859	0.190726575	SLC25A12	1
GO:0035988	Chondrocyte proliferation	1/38	19/18866	0.037601625	0.22932859	0.190726575	STC1	1
GO:0060252	Positive regulation of glial cell proliferation	1/38	19/18866	0.037601625	0.22932859	0.190726575	MYB	1
GO:0090026	Positive regulation of monocyte chemotaxis	1/38	19/18866	0.037601625	0.22932859	0.190726575	SERPINE1	1
GO:0002544	Chronic inflammatory response	1/38	20/18866	0.039542047	0.232485102	0.193351763	TNFAIP3	1
GO:0032495	Response to muramyl dipeptide	1/38	20/18866	0.039542047	0.232485102	0.193351763	TNFAIP3	1
GO:0034138	Toll-like receptor 3 signaling pathway	1/38	20/18866	0.039542047	0.232485102	0.193351763	TNFAIP3	1
GO:0071636	Positive regulation of transforming growth factor beta production	1/38	20/18866	0.039542047	0.232485102	0.193351763	MYB	1
GO:2001169	Regulation of ATP biosynthetic process	1/38	20/18866	0.039542047	0.232485102	0.193351763	SLC25A12	1
GO:0006959	Humoral immune response	3/38	377/18866	0.039894013	0.232485102	0.193351763	CXCL3/PPBP/CXCL2	3
GO:0002029	Desensitization of G protein-coupled receptor signaling pathway	1/38	21/18866	0.04147866	0.232485102	0.193351763	APLN	1
GO:0022401	Negative adaptation of signaling pathway	1/38	21/18866	0.04147866	0.232485102	0.193351763	APLN	1
GO:0034471	ncRNA 5′-end processing	1/38	21/18866	0.04147866	0.232485102	0.193351763	POP1	1
GO:0072574	Hepatocyte proliferation	1/38	21/18866	0.04147866	0.232485102	0.193351763	TNFAIP3	1
GO:0072575	Epithelial cell proliferation involved in liver morphogenesis	1/38	21/18866	0.04147866	0.232485102	0.193351763	TNFAIP3	1
GO:0090280	Positive regulation of calcium ion import	1/38	21/18866	0.04147866	0.232485102	0.193351763	STC1	1
GO:0098780	Response to mitochondrial depolarisation	1/38	21/18866	0.04147866	0.232485102	0.193351763	TOMM7	1
GO:1903599	Positive regulation of autophagy of mitochondrion	1/38	21/18866	0.04147866	0.232485102	0.193351763	TOMM7	1
GO:0007398	Ectoderm development	1/38	22/18866	0.04341147	0.232485102	0.193351763	KRT6B	1
GO:0023058	Adaptation of signaling pathway	1/38	22/18866	0.04341147	0.232485102	0.193351763	APLN	1
GO:0034104	Negative regulation of tissue remodeling	1/38	22/18866	0.04341147	0.232485102	0.193351763	TNFAIP3	1
GO:0044342	Type B pancreatic cell proliferation	1/38	22/18866	0.04341147	0.232485102	0.193351763	IGFBP3	1
GO:0045624	Positive regulation of T-helper cell differentiation	1/38	22/18866	0.04341147	0.232485102	0.193351763	MYB	1
GO:0045663	Positive regulation of myoblast differentiation	1/38	22/18866	0.04341147	0.232485102	0.193351763	IGFBP3	1
GO:0072576	Liver morphogenesis	1/38	22/18866	0.04341147	0.232485102	0.193351763	TNFAIP3	1
GO:0000966	RNA 5′-end processing	1/38	23/18866	0.045340485	0.232485102	0.193351763	POP1	1
GO:0006359	Regulation of transcription by RNA polymerase III	1/38	23/18866	0.045340485	0.232485102	0.193351763	POLR3G	1
GO:0015813	l-glutamate transmembrane transport	1/38	23/18866	0.045340485	0.232485102	0.193351763	SLC25A12	1
GO:0031639	Plasminogen activation	1/38	23/18866	0.045340485	0.232485102	0.193351763	SERPINE1	1
GO:0032703	Negative regulation of interleukin-2 production	1/38	23/18866	0.045340485	0.232485102	0.193351763	TNFAIP3	1
GO:0042026	Protein refolding	1/38	23/18866	0.045340485	0.232485102	0.193351763	HSPA1B	1
GO:0042401	Cellular biogenic amine biosynthetic process	1/38	23/18866	0.045340485	0.232485102	0.193351763	SRM	1
GO:0043576	Regulation of respiratory gaseous exchange	1/38	23/18866	0.045340485	0.232485102	0.193351763	APLN	1
GO:0051570	Regulation of histone H3-K9 methylation	1/38	23/18866	0.045340485	0.232485102	0.193351763	MYB	1
GO:0040013	Negative regulation of locomotion	3/38	397/18866	0.045353407	0.232485102	0.193351763	IGFBP3/STC1/SERPINE1	3
GO:0034614	Cellular response to reactive oxygen species	2/38	170/18866	0.04592247	0.232485102	0.193351763	TNFAIP3/MYB	2
GO:0051271	Negative regulation of cellular component movement	3/38	400/18866	0.046203141	0.232485102	0.193351763	IGFBP3/STC1/SERPINE1	3
GO:0051302	Regulation of cell division	2/38	171/18866	0.046408056	0.232485102	0.193351763	PPBP/KIF18B	2
GO:0002244	Hematopoietic progenitor cell differentiation	2/38	172/18866	0.046895559	0.232485102	0.193351763	MYB/KRT75	2
GO:0009309	Amine biosynthetic process	1/38	24/18866	0.047265713	0.232485102	0.193351763	SRM	1
GO:0034143	Regulation of toll-like receptor 4 signaling pathway	1/38	24/18866	0.047265713	0.232485102	0.193351763	TNFAIP3	1
GO:0044062	Regulation of excretion	1/38	24/18866	0.047265713	0.232485102	0.193351763	STC1	1
GO:0051446	Positive regulation of meiotic cell cycle	1/38	24/18866	0.047265713	0.232485102	0.193351763	CDC25A	1
GO:0070841	Inclusion body assembly	1/38	24/18866	0.047265713	0.232485102	0.193351763	HSPA1B	1
GO:0090169	Regulation of spindle assembly	1/38	24/18866	0.047265713	0.232485102	0.193351763	HSPA1B	1
GO:0033209	Tumor necrosis factor-mediated signaling pathway	2/38	173/18866	0.047384968	0.232485102	0.193351763	TNFAIP3/HSPA1B	2
GO:0016241	Regulation of macroautophagy	2/38	176/18866	0.048864544	0.232485102	0.193351763	TOMM7/PIM2	2
GO:0000423	Mitophagy	1/38	25/18866	0.04918716	0.232485102	0.193351763	TOMM7	1
GO:0002092	Positive regulation of receptor internalization	1/38	25/18866	0.04918716	0.232485102	0.193351763	APLN	1
GO:0015740	C4-dicarboxylate transport	1/38	25/18866	0.04918716	0.232485102	0.193351763	SLC25A12	1
GO:0046697	Decidualization	1/38	25/18866	0.04918716	0.232485102	0.193351763	STC1	1
GO:0050927	Positive regulation of positive chemotaxis	1/38	25/18866	0.04918716	0.232485102	0.193351763	S1PR1	1
GO:0071677	Positive regulation of mononuclear cell migration	1/38	25/18866	0.04918716	0.232485102	0.193351763	SERPINE1	1
GO:1905564	Positive regulation of vascular endothelial cell proliferation	1/38	25/18866	0.04918716	0.232485102	0.193351763	APLN	1
GO:0048771	Tissue remodeling	2/38	178/18866	0.049860292	0.232485102	0.193351763	TNFAIP3/S1PR1	2

Table S6.

Functional enrichment analysis (MF) of the genes associated with the upregulated genes

ID	Description	GeneRatio	BgRatio	p-value	p.adjust	q-value	geneID	Count
GO:0001664	G protein-coupled receptor binding	7/40	293/18352	2.92192E-06	0.000514258	0.000387539	CXCL3/PPBP/CXCL2/APLN/S1PR1/DNAJA1/HSPA1B	7
GO:0045236	CXCR chemokine receptor binding	3/40	18/18352	7.6518E-06	0.000673358	0.000507435	CXCL3/PPBP/CXCL2	3
GO:0008009	Chemokine activity	3/40	49/18352	0.000164861	0.009671818	0.007288571	CXCL3/PPBP/CXCL2	3
GO:0042379	Chemokine receptor binding	3/40	70/18352	0.000474548	0.020880096	0.015735001	CXCL3/PPBP/CXCL2	3
GO:0005520	Insulin-like growth factor binding	2/40	29/18352	0.001811907	0.063779118	0.048063211	IGFBP3/ESM1	2
GO:0031072	Heat shock protein binding	3/40	127/18352	0.002652501	0.072483606	0.054622813	CHORDC1/DNAJA1/HSPA1B	3
GO:0005178	Integrin binding	3/40	144/18352	0.003779843	0.072483606	0.054622813	ESM1/TLN2/TGFBI	3
GO:0031625	Ubiquitin protein ligase binding	4/40	297/18352	0.003884332	0.072483606	0.054622813	FZD8/UBE2D4/DNAJA1/HSPA1B	4
GO:0048018	Receptor ligand activity	5/40	487/18352	0.003943689	0.072483606	0.054622813	CXCL3/PPBP/CXCL2/APLN/STC1	5
GO:0030546	Signaling receptor activator activity	5/40	492/18352	0.004118387	0.072483606	0.054622813	CXCL3/PPBP/CXCL2/APLN/STC1	5
GO:0044389	Ubiquitin-like protein ligase binding	4/40	316/18352	0.004838462	0.077415397	0.058339354	FZD8/UBE2D4/DNAJA1/HSPA1B	4
GO:0005125	Cytokine activity	3/40	235/18352	0.014454634	0.16029063	0.120793178	CXCL3/PPBP/CXCL2	3
GO:0004725	Protein tyrosine phosphatase activity	2/40	101/18352	0.020420482	0.16029063	0.120793178	CDC25A/CDKN3	2
GO:0005126	Cytokine receptor binding	3/40	271/18352	0.021045942	0.16029063	0.120793178	CXCL3/PPBP/CXCL2	3
GO:0005200	Structural constituent of cytoskeleton	2/40	104/18352	0.02156948	0.16029063	0.120793178	KRT6B/TLN2	2
GO:0051087	Chaperone binding	2/40	104/18352	0.02156948	0.16029063	0.120793178	CDC25A/DNAJA1	2
GO:0018455	Alcohol dehydrogenase [NAD(P)+] activity	1/40	10/18352	0.02158869	0.16029063	0.120793178	DHRS9	1
GO:0030957	Tat protein binding	1/40	10/18352	0.02158869	0.16029063	0.120793178	DNAJA1	1
GO:0033204	Ribonuclease P RNA binding	1/40	10/18352	0.02158869	0.16029063	0.120793178	POP1	1
GO:0004222	Metalloendopeptidase activity	2/40	108/18352	0.023142512	0.16029063	0.120793178	ADAMTS6/ADAMTS14	2
GO:0008525	Phosphatidylcholine transporter activity	1/40	11/18352	0.023722397	0.16029063	0.120793178	PITPNM2	1
GO:0004526	Ribonuclease P activity	1/40	12/18352	0.025851567	0.16029063	0.120793178	POP1	1
GO:0061578	Lys63-specific deubiquitinase activity	1/40	12/18352	0.025851567	0.16029063	0.120793178	TNFAIP3	1
GO:0051082	Unfolded protein binding	2/40	118/18352	0.027274787	0.16029063	0.120793178	DNAJA1/HSPA1B	2
GO:0031994	Insulin-like growth factor I binding	1/40	13/18352	0.027976209	0.16029063	0.120793178	IGFBP3	1
GO:0072542	Protein phosphatase activator activity	1/40	13/18352	0.027976209	0.16029063	0.120793178	IGFBP3	1
GO:0005179	Hormone activity	2/40	122/18352	0.029005294	0.16029063	0.120793178	APLN/STC1	2
GO:0005313	l-glutamate transmembrane transporter activity	1/40	14/18352	0.030096333	0.16029063	0.120793178	SLC25A12	1
GO:0004549	tRNA-specific ribonuclease activity	1/40	15/18352	0.032211948	0.16029063	0.120793178	POP1	1
GO:0042813	Wnt-activated receptor activity	1/40	15/18352	0.032211948	0.16029063	0.120793178	FZD8	1
GO:0005229	Intracellular calcium activated chloride channel activity	1/40	16/18352	0.034323063	0.16029063	0.120793178	TTYH2	1
GO:0008574	ATP-dependent microtubule motor activity, plus-end-directed	1/40	16/18352	0.034323063	0.16029063	0.120793178	KIF18B	1
GO:0015172	Acidic amino acid transmembrane transporter activity	1/40	16/18352	0.034323063	0.16029063	0.120793178	SLC25A12	1
GO:0015556	C4-dicarboxylate transmembrane transporter activity	1/40	16/18352	0.034323063	0.16029063	0.120793178	SLC25A12	1
GO:0019211	Phosphatase activator activity	1/40	16/18352	0.034323063	0.16029063	0.120793178	IGFBP3	1
GO:0045125	Bioactive lipid receptor activity	1/40	16/18352	0.034323063	0.16029063	0.120793178	S1PR1	1
GO:0061778	Intracellular chloride channel activity	1/40	16/18352	0.034323063	0.16029063	0.120793178	TTYH2	1
GO:0019838	Growth factor binding	2/40	136/18352	0.035395696	0.16029063	0.120793178	IGFBP3/ESM1	2
GO:0002020	Protease binding	2/40	137/18352	0.035871398	0.16029063	0.120793178	TNFAIP3/SERPINE1	2
GO:0016854	Racemase and epimerase activity	1/40	17/18352	0.036429689	0.16029063	0.120793178	DHRS9	1
GO:0004745	Retinol dehydrogenase activity	1/40	20/18352	0.042722715	0.164575436	0.124022159	DHRS9	1
GO:0008320	Protein transmembrane transporter activity	1/40	20/18352	0.042722715	0.164575436	0.124022159	TOMM7	1
GO:0140318	Protein transporter activity	1/40	20/18352	0.042722715	0.164575436	0.124022159	TOMM7	1
GO:0005355	Glucose transmembrane transporter activity	1/40	21/18352	0.044811472	0.164575436	0.124022159	PPBP	1
GO:0015149	Hexose transmembrane transporter activity	1/40	21/18352	0.044811472	0.164575436	0.124022159	PPBP	1
GO:0050750	Low-density lipoprotein particle receptor binding	1/40	21/18352	0.044811472	0.164575436	0.124022159	DNAJA1	1
GO:0070530	K63-linked polyubiquitin modification-dependent protein binding	1/40	21/18352	0.044811472	0.164575436	0.124022159	TNFAIP3	1
GO:0022884	Macromolecule transmembrane transporter activity	1/40	22/18352	0.046895785	0.164575436	0.124022159	TOMM7	1
GO:0120014	Phospholipid transfer activity	1/40	22/18352	0.046895785	0.164575436	0.124022159	PITPNM2	1
GO:0015145	Monosaccharide transmembrane transporter activity	1/40	23/18352	0.048975663	0.164575436	0.124022159	PPBP	1

Table S7.

Functional enrichment analysis (CC) of the DEGs associated with the upregulated genes

ID	Description	GeneRatio	BgRatio	p-value	p.adjust	q-value	geneID	Count
GO:0031093	Platelet alpha granule lumen	2/39	67/19559	0.007893629	0.247850692	0.220518786	PPBP/SERPINE1	2
GO:0031091	Platelet alpha granule	2/39	91/19559	0.01418764	0.247850692	0.220518786	PPBP/SERPINE1	2
GO:0045095	Keratin filament	2/39	95/19559	0.015392516	0.247850692	0.220518786	KRT6B/KRT75	2
GO:0030681	Multimeric ribonuclease P complex	1/39	10/19559	0.019766209	0.247850692	0.220518786	POP1	1
GO:0000235	Astral microtubule	1/39	11/19559	0.021721763	0.247850692	0.220518786	KIF18B	1
GO:0002177	Manchette	1/39	11/19559	0.021721763	0.247850692	0.220518786	STRBP	1
GO:0005818	Aster	1/39	11/19559	0.021721763	0.247850692	0.220518786	KIF18B	1
GO:0030677	Ribonuclease P complex	1/39	14/19559	0.027565644	0.247850692	0.220518786	POP1	1
GO:1990023	Mitotic spindle midzone	1/39	14/19559	0.027565644	0.247850692	0.220518786	KIF18B	1
GO:0098554	Cytoplasmic side of endoplasmic reticulum membrane	1/39	15/19559	0.029506035	0.247850692	0.220518786	DNAJA1	1
GO:0005666	RNA polymerase III complex	1/39	18/19559	0.035304599	0.269598759	0.23986857	POLR3G	1
GO:0035371	Microtubule plus-end	1/39	23/19559	0.044893941	0.285010639	0.253580895	KIF18B	1
GO:0098799	Outer mitochondrial membrane protein complex	1/39	24/19559	0.046800633	0.285010639	0.253580895	TOMM7	1

Table S8.

Functional enrichment analysis (KEGG) of genes associated with the upregulated genes

ID	Description	GeneRatio	BgRatio	p-value	p.adjust	q-value	geneID	Count
hsa05134	Legionellosis	3/21	57/8223	0.000384425	0.027678575	0.022256164	CXCL3/CXCL2/HSPA1B	3
hsa04657	IL-17 signaling pathway	3/21	94/8223	0.001657299	0.039867397	0.032057118	CXCL3/TNFAIP3/CXCL2	3
hsa04061	Viral protein interaction with cytokine and cytokine receptor	3/21	100/8223	0.001979642	0.039867397	0.032057118	CXCL3/PPBP/CXCL2	3
hsa04064	NF-kappa B signaling pathway	3/21	104/8223	0.002214855	0.039867397	0.032057118	CXCL3/TNFAIP3/CXCL2	3
hsa04668	TNF signaling pathway	3/21	114/8223	0.002877066	0.041429752	0.033313397	CXCL3/TNFAIP3/CXCL2	3
hsa04218	Cellular senescence	3/21	156/8223	0.006931269	0.083175226	0.066880664	IGFBP3/CDC25A/SERPINE1	3
hsa04141	Protein processing in endoplasmic reticulum	3/21	171/8223	0.008922601	0.091775328	0.073795951	UBE2D4/DNAJA1/HSPA1B	3
hsa04621	NOD-like receptor signaling pathway	3/21	186/8223	0.011219936	0.095815294	0.077044462	CXCL3/TNFAIP3/CXCL2	3
hsa04062	Chemokine signaling pathway	3/21	192/8223	0.012226679	0.095815294	0.077044462	CXCL3/PPBP/CXCL2	3
hsa05120	Epithelial cell signaling in Helicobacter pylori infection	2/21	70/8223	0.013513912	0.095815294	0.077044462	CXCL3/CXCL2	2
hsa04115	p53 signaling pathway	2/21	73/8223	0.014638448	0.095815294	0.077044462	IGFBP3/SERPINE1	2
hsa05417	Lipid and atherosclerosis	3/21	215/8223	0.016561503	0.099369018	0.079901988	CXCL3/CXCL2/HSPA1B	3
hsa05323	Rheumatoid arthritis	2/21	93/8223	0.023111727	0.128003412	0.102926721	CXCL3/CXCL2	2
hsa05146	Amoebiasis	2/21	102/8223	0.027448456	0.141163486	0.113508651	CXCL3/CXCL2	2
hsa04060	Cytokine-cytokine receptor interaction	3/21	295/8223	0.037680574	0.180866757	0.145433796	CXCL3/PPBP/CXCL2	3
hsa04371	Apelin signaling pathway	2/21	139/8223	0.048309475	0.200783275	0.16144854	APLN/SERPINE1	2
hsa05162	Measles	2/21	139/8223	0.048309475	0.200783275	0.16144854	TNFAIP3/HSPA1B	2

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DOI: https://doi.org/10.2478/aite-2024-0022 | Journal eISSN: 1661-4917

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Language: English

Submitted on: Jul 22, 2024

Accepted on: Sep 26, 2024

Published on: Nov 1, 2024

Published by: Hirszfeld Institute of Immunology and Experimental Therapy

In partnership with: Paradigm Publishing Services

Publication frequency: 1 issue per year

Keywords:

Ado-Met,

PC-3 cells,

miRNAs,

TGF-beta pathway

Related subjects:

Medicine,

Basic medical science,

Biochemistry,

Immunology,

Clinical medicine,

Clinical medicine, other,

Clinical chemistry

© 2024 Thomas Schmidt, published by Hirszfeld Institute of Immunology and Experimental Therapy
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

Volume 72 (2024): Issue 1 (January 2024)

S-Adenosylmethionine Treatment Diminishes the Proliferation of Castration-Resistant Prostate Cancer Cells by Modulating the Expression of miRNAs

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