RNA-seq Analysis of Spaceflown Mouse Lungs Reveals Changes in Circadian Gene Expression

Despite the decades that have passed since the last lunar landing, the elevated risk of developing cancer post-flight persists as a threat to astronaut health. High doses of ionizing radiation experienced during spaceflight exposure beyond low-Earth orbit (LEO) are a large contributing factor to cancer risk due to radiation-induced DNA damage. However, circadian rhythm disruption resulting from spaceflight-induced stress may serve to augment such radiation-induced harm. Upon re-analysis of “GLDS-248: The Transcriptional Analysis of Lung From Mice Flown on the RR-6 Mission” from the NASA GeneLab data repository, six circadian genes were differentially expressed as a result of spaceflight conditions. One such gene found to be up-regulated in relation to ground control was Arntl, which plays a crucial role in regulating cell cycle progression as a core clock gene. Others included Npas2 (up-regulated), which functions similarly to Arntl, and Per3 (down-regulated), which regulates Arntl activity. Due to these results, we hypothesize that circadian rhythm disruption during spaceflight heightens radiation-induced DNA damage due to impaired DNA repair pathways, thus inducing tumorigenesis. This paper seeks to elucidate how transcriptional regulation of the circadian clock influences cancer prognosis during spaceflight exposure, an increasingly relevant research area as NASA focuses beyond the LEO and exposure to galactic cosmic radiation becomes an increasingly significant concern to astronaut health.