MitomiRs: their roles in mitochondria and importance in cancer cell metabolism

Rencelj, Andrej; Gvozdenovic, Nada; Cemazar, Maja

doi:10.2478/raon-2021-0042

Figures & Tables

Canonical biosynthesis of miRNAs/mitomiRs (adopted from 29, 43, 45). Mature miRNA can be transported into any part of the cell; but miRNA/mitomiR regulation is possible only after incorporation into RISC. (AGO2 = argonaute 2; DGCR8 = DiGeorge critical region 8; EXP5 = exportin 5; GTP = guanosine triphosphate; IMP8 = importin 8; mRISC = RNA induced silencing complex loaded with mature miRNA; POLII = DNA polymerase II; RANGTP = binding nuclear protein RAN; RISC = RNA-induced silencing complex; TRBP2 = RISC-loading complex subunit TRBP2).

The network of the mitomiRs and their target genes (grey rectangle) in primates (data from Table 1). Blue arrows present downregulation, green arrows present upregulation and black T-line present silencing. Purple octagon shape presents monkey miRNA and cyan hexagon presents human miRNAs (figure constructed with Cytoscape Network Data Integration, Analysis, and Visualization in a Box V3.8.2).

The network of the mitomiRs and their target genes (grey rectangle) in rodents (data from Table 1). Blue arrows present downregulation and green arrows present upregulation. Orange diamond shape presents rat miRNAs, yellow rectangle presents mouse miRNAs and cyan hexaon presents human miRNAs. miR-199a and miR-143 show that this two miRNAs regulate (figure constructed with Cytoscape Network Data Integration, Analysis, and Visualization in a Box V3.8.2).

Summary of microRNAs and their roles in mitochondria

miR	miR accession number	Target genes	Gene accession number	Function	Functional pathway	Location	Species	References
miR-378	MI0000795	Crat	ENSMUSG00000026853	Downregulation	Mitochondrial oxidative metabolism	Mitochondria in liver cells	Mouse	Carrer et al., 201259
miR-24	MI0000080	H2ax	ENSMUSG00000049932	Downregulation	Insulin pathway signaling	Mitochondria liver cells in	Human	Jeong et al., 201761
miR-23b	MI0000439	GLS	ENSG00000115419	Downregulation	Glutamine metabolism	LMitochondria liver cells in	Human	Gao et al., 200960
		SLC2A1	ENSG00000117394	Downregulation
miR-1291	MI0006353	CPT1C ESRRA	ENSG00000169169 ENSG00000173153	Downregulation Downregulation	Mitochondrial	Mitochondria in	Human	Yamasaki et al., 2013; Chen et al.,
		ASS1	ENSG00000130707	Downregulation	metabolism	renal cells		2020, Tu et al., 202063, 64, 65
		GLUT1	ENSG00000117394	Downregulation
miR-138	MI0000455	PDK1	ENSG00000152256	Downregulation	Glucose metabolism	Mitochondria in cardiac cells	Human	Zhu et al., 201766
miR-150	MI0000920 MI0000479	Slc2a4 SLC2A1	ENSRNOG00000017226 ENSG00000117394	Downregulation Downregulation	Metabolism	Mitochondria in cardiac cells	Rat Human	Ju et al., 202067 Li et al., 201768
		Slc2a4	ENSRNOG00000017226	Upregulation		Mitochondria in
miR-199a	MI0000941	Hk2	ENSRNOG00000006116	Upregulation	Expression of	muscle cells	Rat	Esteves et al., 2018, Yan et al., 2014, Guo
	MI0000242	HK2	ENSG00000159399	Upregulation	glucose transporters	Mitochondria in liver cells	Human	et al., 20154, 69, 70
miR-532-5p	MI0006154	SlcHk22 a4	ENSRNOGENSRNOG00000017226 00000006116	Upregulation Upregulation	Expression glucose transporters of	Mitochondria muscle cells in	Rat	Esteves et al., 201870
					Mitochondrial	Mitochondria in
miR-29a	MI0000576	Slc16a1	ENSMUSG00000032902	Downregulation	oxidative metabolism	pancreatic betacells	Mouse	Pullen et al., 201171
miR-29b	MI0000143	Slc16a1	ENSMUSG00000032902	Downregulation	Mitochondrial oxidative metabolism	Mitochondria in pancreatic betacells	Mouse	Pullen et al., 201171
					Mitochondrial	Mitochondria in
miR-124	MI0000716	Slc16a1	ENSMUSG00000032902	Downregulation	oxidative	pancreatic beta-	Mouse	Pullen et al., 201171
					metabolism	cells
		CROT	ENSANAG00000028065	Downregulation
		CPT1A	ENSANAG00000017356	Downregulation
		HADHB	ENSANAG00000027802	Downregulation
		PRKAA1	ENSANAG00000032687	Downregulation
miR-33a/b	a-MI0002684, b-MI0007603	ABCA1	ENSANAG00000033387	Downregulation	Lipid metabolism	Mitochondria in liver cells	Monkey	Rayner et al., 201172
		SREBF1	ENSANAG00000021477	Upregulation
		FASN	ENSANAG00000032055	Upregulation
		ACLY	ENSANAG00000036009	Upregulation
		ACACA	ENSANAG00000035253	Upregulation
miR-143	MI0000916	Map2k5	ENSRNOG00000007926	Downregulation	Adipogenesis	Mitochondria in adipose cells	Rat	Chen et al., 201473
	MI0000459	APOL6	ENSG00000221963	Downregulation	Adpiogenesis	Mitochondria in adipose cells	Human	Ye et al., 201374
miR-204	MI0000284	ACACB	ENSG00000076555	Downregulation	Lipid metabolism	Mitochondria adipose cells in	Human	Civelek et al., 201375
miR-200	MI0000737	ZEBZEB1 2	ENSGENSG00000148516 00000169554	Upregulation Upregulation	Lipid metabolism	Mitochondria breast cells in	Human	Ahmad et al., 201176
miR-338	MI0000618	COXIV	ENSRNOG00000007827	Downregulation	Mitochondria oxidative metabolism	Mitochondria in neural cells	Rat	Aschrafi et al., 200877
miR-181c	MI0000924	COX1	ENSRNOG00000034234	Downregulation	Mitochondria oxidative metabolism	Mitochondria in cardiac cells	Rat	Das et al., 201288
miR-210	MI0000268	ISCU	ENSG00000136003	Downregulation	Mitochondria oxidative metabolism	Mitochondria in placenta cells	Human	Colleoni et al., 2013; Qiao et al., 201381, 85
miR-15b	MI0000843	Arl2	ENSRNOG00000021010	Downregulation	ATP production	Mitochondria in cardiac cells	Rat	Nishi et al., 201082
		Bcl2	ENSRNOG00000002791	Downregulation
miR-16	MI0000844	Bcl2	ENSRNOG00000002791	Downregulation	ATP production	Mitochondria in cardiac cells	Rat	Nishi et al., 201082
		Arl2	ENSRNOG00000021010	Downregulation
miR-195	MI0000939	Arl2	ENSRNOG00000021010	Downregulation	ATP production	Mitochondria in cardiac cells	Rat	Nishi et al., 201082
miR-29a-3p	MI0000576	Foxa2	ENSMUSG00000037025	Upregulation	Lipid metabolism	Mitochondria liver cells in	Mouse	Kurtz et al., 201486
miR-19b	MI0000074	MFN1	ENSG00000171109	Downregulation	Apoptosis	Mitochondria in bone cells	Human	Li et al., 201487
miR-101-3p	MI0000103	ATP5B	ENSG00000110955	Silencing	Mitochondria metabolism	Mitochondria heLa cells in	Human	Zheng et al., 201184

Summary of mitomiRs with roles in cancer

miR	miR accession number	Target genes	Gene accession number	Function	Functional pathway	Type of cancer	Species	References
		HIF-1	ENSG00000258777	Upregulation
		ISCU	ENSG00000136003	Upregulation
miR-210	MI0000286	COX10	ENSG00000006695	Upregulation	Hypoxia	Breast cancer, neck and head cancer, lung cancer	Human	Qin et al., 2014; Gee et al., 2010; Puissegur et al., 2011109, 110, 111
		SDHD	ENSG00000204370	Upregulation
		NDUFA4	ENSG00000189043	Upregulation
miR-200a	MI0000342	TFAM	ENSG00000108064	Downregulation	Mitochondrial biogenesis, cancer metabolism	Breast cancer	Human	Yao et al., 2014112
miR-155	MI0000681	HK2	ENSG00000159399	Upregulation	phosphorylation Glucose	Breast cancer	Human	Jiang Fang et et al.al., , 20122012; 104
miR-124	MI0000443	PKM	ENSG00000067225	Upregulation	metabolism Glucose	Colorectal cancer	Human	Sun et al., 2012105
miR-137	MI0000454	PKM	ENSG00000067225	Upregulation	metabolism Glucose	Colorectal cancer	Human	Sun et al., 2012105
miR-340	MI0000802	PKM	ENSG00000067225	Upregulation	metabolism Glucose	Colorectal cancer	Human	Sun et al., 2012105
miR-326	MI0000808	PKM2	ENSG00000067225	Downregulation	metabolism Glucose	Glioblastoma	Human	Kefas et al., 2010106
miR-181-5p	MIMAT0000256	RASSF6INPP5A	ENSG00000169435ENSG00000068383	DownregulationDownregulation	Mitogen-activated protein kinase (MAPK) signaling pathway	Gastric cancer, cervical cancer	Human	Mi et al., 2017; Zhuang et al., 2017108, 113
miR-92a-1	MI0000093	BCL2L11	ENSG00000153094	Downregulation	Apoptosis	Lymphoma	Human	Mogilyansky Rigoutsos, 2013 and 94
		PIK3R2	ENSG00000105647	Downregulation		Breast cancer cells		Zhu et al., 2011114
		PLK2	ENSG00000260410	Downregulation		Acute leukaemia cells		Li et al., 2008115
		EGFL7	ENSG00000172889	Downregulation		Oral squamous cells		Sasahira et al., 2012116
		CRK	ENSG00000167193	Downregulation		Lung cancer cells		Crawford 2008117 et al.,
		ADAM9	ENSG00000168615	Downregulation		Melanoma cells cancer		Felli et al., 2013118
miR-126	MI0000471	HOXA9	ENSG00000078399	Downregulation	Inflammation, angiogenesis	Acute leukaemia cells	Human	Shen et al., 2008119
		IRS1	ENSG00000169047	Downregulation		Breast cancer cells		Zhang et al., 2008120
		SOX-2	ENSG00000242808	Downregulation		Gastric cells cancer		Otsubo et al., 2011121
		SLC7A5	ENSG00000103257	Downregulation		Lung cancer cells		Miko et al., 2011122
		VEGFA	ENSG00000150630	Downregulation		Oral squamous cells		Sasahira et al., 2012116
		MMP7	ENSG00000137673	Downregulation		Melanoma cells cancer		Felli et al., 2013118
		BCL-2	ENSG00000171791	Downregulation
								Gao et al., 2010101
		MCL-1	ENSG00000143384	Downregulation
		COX4I2	ENSG00000131055	Downregulation
miR-15a	MI0000069	COX6A2	ENSG00000156885	Downregulation	Apoptosis, ATP production	B-cell chronic lymphocytic leukemia	Human	Siengdee et al.,
		NDUFB7	ENSG00000099795	Downregulation				2010102
		NDUFV1	ENSG00000167792	Downregulation
		NDUFS4	ENSG00000164258	Downregulation
		COX4I2	ENSG00000131055	Downregulation
		COX6A2	ENSG00000156885	Downregulation
miR-16a	MI0000070	NDUFB7	ENSG00000099795	Downregulation	Apoptosis, ATP production	B-lymphocytic cell chronic leukemia	Human	Siengdee et al., 2010102
		NDUFV1	ENSG00000167792	Downregulation
		NDUFS4	ENSG00000164258	Downregulation

MitomiRs: their roles in mitochondria and importance in cancer cell metabolism

Figures & Tables

Figure 1

Figure 2

Figure 3

Figure 4

Summary of microRNAs and their roles in mitochondria

Summary of mitomiRs with roles in cancer

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