CircFUT8 Promotes Hepatocellular Carcinoma Progression By Targeting The MiR-548c/FUT8 Axis

Background:Liver cancer is one of the most common malignancies in the world.Although treatments have become more diverse in recent years,morbidity and mortality remain high.Among them,Hepatocellular carcinoma(HCC)accounts for the largest proportion,which has attracted widespread attention from scientists.Therefore,it is necessary to explore the molecular mechanism of the occurrence and development of HCC and discover new therapeutic targets or prognostic markers in order to achieve its early diagnosis and accurate treatment.Circular RNA is a new type of covalently closed endogenous non-coding RNA.It may play a role in many processes in tumors and often acts as a miRNA sponge to regulate the expression of cancer-related genes.Fucosyltransferase 8(FUT8)participates in the core fucosylation process.It is essential for E-cadherin-mediated intercellular adhesion,and its expression may have certain regulatory effects on the invasion and metastasis ability of cancer cells.In this study,based on previous experiments,we propose the hypothesis that the circular RNA circFUT8 may regulate the development of hepatocellular carcinoma through the miR-548c / FUT8 axis,and analyze the circFUT8 / miR-548c / FUT8 module for hepatocellular carcinoma Impact of migration and invasion capabilities.The above provides new ideas for finding new diagnostic methods,prognostic markers and stable therapeutic targets.Method:Based on the module screened by the research team in the early stage of bioinformatics,we use a large number of molecular biology techniques to verify that circFUT8 may regulate the development mechanism of hepatocellular carcinoma through the miR-548c / FUT8 axis.CircFUT8 / miR-548c / FUT8 modules are mainly explained in vivo and in vitro through a large number of functional experiments such as fluorescence in situ hybridization,RNA immunoprecipitation,CCK8,Western Blot,dual luciferase gene reporting,and tumor formation in nude mice.Impact on hepatocellular carcinoma.To elucidate the molecular mechanism of cFUT8 acting as miR-548c sponge and regulating FUT8 expression during HCC epithelial-mesenchymal transition.Results:It was found in the in vitro cell experiment system that inhibition of FUT8 significantly reduced cell adhesion and inhibited cell migration and invasion.In vivo experiments confirmed that inhibition of FUT8 will inhibit tumor growth.The subcellular location of cFUT8 was detected by FISH and found to be mainly located in the cytoplasm of HCC.Through experiments such as RNA immunoprecipitation and dual luciferase gene reporting,it was verified that endogenous cFUT8 is a binding platform for miR548c,and FUT8 is a direct target of miR-548c.By absorbing free miR-548c in the cytoplasm,cFUT8 may indirectly control FUT8 expression.In clinical samples and cell lines,it was verified that cFUT8 expression level was positively correlated with FUT8 expression and positively correlated with the degree of malignancy.The expression of circular RNA FUT8 changes,which affects the change of FUT8 through miR-548c,and affects the process of epithelial mesenchymal transformation through E-cadherin/?-catenin/LEF-1 signaling.Conclusion:1.FUT8 can promote the proliferation,invasion and migration of hepatocellular carcinoma cells.2.CircFUT8 regulates the progression of hepatocellular carcinoma through miR-548c/FUT8.3.The cFUT8/ miR-548c /FUT8 regulation axis can regulate EMT process through E-cadherin/?-catenin/LEF-1 signal.