CircGNAO1 strengthens its host gene GNAO1 expression for suppression of hepatocarcinogenesis.

ABSTRACT

Background: Hepatocellular carcinoma (HCC) is one of the most prevalent primary liver carcinoma. Guanine nucleotide-binding protein, α-activating activity polypeptide O (GNAO1) was reported to be under-expressed in HCC tissues. This study aimed to investigate the GNAO1-derived circular RNA (circRNA) and its molecular mechanisms in HCC. Methods: Real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot were applied to examine RNA and protein levels. Functional experiments were performed to study HCC cell proliferation, cell cycle and cellular senescence. The interactions among circGNAO1, GNAO1 and DNA methyltransferase 1 (DNMT1) were examined by mechanism assays. The methylation level was analyzed by bisulfite sequencing PCR (BSP). Results: CircGNAO1 is down-regulated and positively associated with GNAO1 in HCC tissues. Overexpression of circGNAO1 inhibits cell proliferation, induces cell cycle arrest and facilitates cell senescence in HCC cells. CircGNAO1 facilitates the progression of HCC via modulating GNAO1. Mechanistically, circGNAO1 enhances the transcription of GNAO1 by sequestering DNMT1, thereby up-regulating GNAO1 expression in HCC cells. Conclusions: CircGNAO1 up-regulates its host gene GNAO1 expression for suppression of hepatocarcinogenesis.