HNF4G Influences The Proliferation And Migration Of Gallbladder Cancer Cells And These Related Mechanisms

Objective:To investigate the effect of hepatocyte nuclear factor 4 gamma(HNF4G)expression on the proliferation and migration of gallbladder cancer cells and underlying molecular mechanisms.。Methods:Real-time fluorescence quantitative PCR(q PCR)and western blotting(WB)were used to measure the mRNA and protein expression levels.CCK8 and colony formation assays were applied for cell proliferation detection,while Flow Cytometry for cell cycle and apoptosis analysis.Transwell chamber assay was used to detect the migration ability of gallbladder cancer cells.Results:The q PCR results demonstrated that the expression level of HNF4 G was lower in cancer tissues than in para-carcinoma tissues,but higher in liver metastases than in para-carcinoma tissues.q PCR and WB results showed that the expression levels of HNF4 G mRNA and protein were significantly lower in NOZ cell lines than in GBC-SD and ZJU-0430 cell lines(P <0.05).Sanger sequencing and WB results demonstrated that HNF4 G knockdown and overexpression cell lines were successfully constructed.CCK8 and colony formation assays showed that HNF4 G overexpression enhanced the proliferation and migration abilities of gallbladder cancer cells.HNF4 G overexpression promoted the transition from S-phase to G2/M-phase and inhibited apoptosis.WB indicated that HNF4 G overexpression increased the expression levels of Cyclin A2,Cyclin B1,Bcl-2,N-cadherin,Vimentin,Snail,Slug,and Erb B2 and phosphorylation of Akt.But it decreased the expression levels of Bax and N-cadherin(P<0.05).HNF4 G knockdown caused the opposite effects,resulting in altered biological behavior associated with gallbladder cancer cells.Conclusion:HNF4G affects the proliferation and migration of gallbladder cancer cells by participating in the regulation of the EMT and Erb B2/PI3K/Akt signaling pathways.The importance of HNF4 G in gallbladder cancer suggests that it could be a gene target for gallbladder cancer therapy.