BACKGROUND

Hypoxia is a hallmark of solid cancers, including hepatocellular carcinoma (HCC). There is scarce information about how hypoxia avoids immunologic stress and maintains a cancer-promoting microenvironment.

METHODS

The Cancer Genome Atlas, RNA-seq data, and Oncomine database were used to discover the correlation of with tumor progression; then expression of mRNA and protein were detected in HCC tissues and cells subjected to hypoxia or with the treatment of CoCl via real-time quantitative polymerase chain reaction and immunochemistry assays. Finally, the effect of RNASEH2A on cell proliferation and the involved signaling pathway was explored further.

RESULTS

RNASEH2A was positively correlated with tumor grade, size, vascular invasion, and poor prognosis. The expression of mRNA and protein were increased and dependent on hypoxia-inducible factor 2α in HCC tissues and cell lines. Knockout of in HCC cells greatly reduced cell proliferation and induced the transcription of multiple cGAS-STING (cyclic GMP-AMP synthase-stimulator of interferon genes) targeted type 1 interferon-related genes, including , and , which suggests knockout of may produce immunologic stress and tumor suppressive effects.

CONCLUSIONS

RNASEH2A plays a critical role and potentially predicts patient outcomes in HCC, which uncovers a new mechanism that RNASEH2A contributes to limit immunologic stress of cancer cells in the context of hypoxia.