GNAS promotes inflammation-related hepatocellular carcinoma progression by promoting STAT3 activation

作者：Hongda Ding, Xixia Zhang, Yang Su, Changjun Jia, Chaoliu Dai · 发表于：Cellular & Molecular Biology Letters · 年份：2020 · DOI：10.1186/s11658-020-00204-1 · 被引用次数：101 · 研究领域：RNA modifications and cancer、Genetic Syndromes and Imprinting、Genomics and Rare Diseases

BACKGROUND: Hepatocellular carcinoma (HCC) is still the most common cause of cancer-related mortality worldwide and accumulating studies report that HCC is frequently linked to chronic inflammation. G-protein alpha-subunit (GNAS)-activating mutations have recently been reported to form a rare subgroup of inflammatory liver tumors. In this study, we investigated the roles of GNAS in inflammation-related HCC progression and its underlying mechanism. METHODS: Lipopolysaccharides (LPS) and diethylnitrosamine were employed to stimulate HCC cells to an induced inflammatory response. qRT-PCR, immunohistochemistry and immunoblotting were performed to detect the expression of GNAS in HCC tissues and cell lines. Expression levels of proinflammatory cytokines were detected by qRT-PCR and ELISA. N6-methyladenosine (m6A) methylation of GNAS mRNA was detected by RNA-binding protein immunoprecipitation (RIP). Transcription factors activation profiling plate array was performed to investigate the underlying mechanism in GNAS promoting interleukin-6 (IL-6) expression in HCC cells. HCC cell invasion was determined by transwell assay in vitro, and tumorigenesis was assessed with a subcutaneous xenograft mouse model of HCC. RESULTS: We found that LPS stimulation promotes GNAS expression in HCC cells through increasing m6A methylation of GNAS mRNA. The high expression level of GNAS promotes LPS-induced HCC cell growth and invasion by interacting with signal transducer and activator of transcripti...