Microgravity alleviates low-dose radiation-induced non-targeted carcinogenic effects.

The main hazards astronauts face in space collectively affect their health, especially increasing the carcinogenesis risk. However, it is still unclear how these hazards, especially microgravity and space radiation, induce the carcinogenic transformation of normal cells. In the simulated microgravity (SMG) environment, although radiation could inhibit SMG-accentuated target cell proliferation, increase genomic instability (GI) and carcinogenic transformation rate dose-dependently, we found that for bystander cells, radiation-induced damage could be reduced, GI and the probability of carcinogenic transformation could also be decreased at lower doses (below 0.1 Gy for X-rays and 0.3 Gy for carbon ions). After filtration and KEGG analysis, five differentially expressed genes (DEGs) relating to carcinogenesis were screened out from the transcriptomic sequencing results. Based on the Cancer Genome Atlas (TCGA) from NCI, we found that AREG was closely related to the occurrence and development of lung cancer. Using AREG knockdown or overexpression cell lines, we further validated the significant correlation between abnormal expression of AREG and GI. Our findings indicate that AREG plays a substantial role in GI and carcinogenic transformation following exposure to SMG and radiation.