CircSLC1A4 Mediates N-glycosylation of MUC13 to Promote Cell migration, invasion and EMT in Hepatocellular Carcinoma Through Up-regulation of B4GALT5 Expression

Abstract

Abstract Background: HCC (hepatocellular carcinoma) is the most common type of hepatic cancers with an overall poor prognosis and an alarming rising incidence. There is an urgent need to explore novel therapeutic targets for HCC treatment. Methods: QRT-PCR (quantitative real-time PCR) was applied to analyze the expression level of circSLC1A4 in HCC cell lines. Database analysis, ChIP (chromatin immunoprecipitation), DNA pulldown, RIP (RNA-binding protein immunoprecipitation) and RNA pulldown assays were implemented to investigate the molecular mechanism of circSLC1A4 in HCC. Co-IP (Co-immunoprecipitation) and GST (glutathione S-transferase) pulldown assays were performed to detect the protein-protein interactions. Results: B4GALT5 (beta-1,4-galactosyltransferase 5) promotes cell migration, invasion and EMT (epithelial-mesenchymal transition) in HCC. In addition, the characteristics of circSLC1A4 in HCC were explored. Functionally, circSLC1A4 acts as a tumor-propeller in HCC via regulating B4GALT5. Specifically, circSLC1A4 recruits FOXH1 (forkhead box H1) to stimulate the transcription of B4GALT5 and recruits DDX3X (DEAD-box helicase 3 X-linked) to stabilize B4GALT5 mRNA (messenger RNA). Besides, circSLC1A4 mediates B4GALT5-induced N-glycosylation of MUC13 (mucin 13) and activates Wnt/β-catenin signaling via MUC13. Conclusion: Our study manifested that circSLC1A4 mediates N-glycosylation of MUC13 to promote HCC cell migration, invasion and EMT via up-regulating B4GALT5, offering insight into HCC treatment.