Bioinformatics Analysis Of ZC3H13 And Its Effect On The Biological Behavior Of Hepatocellular Carcinoma

Objective: Patients with hepatocellular carcinoma(HCC)are prone to recurrence or metastasis after surgery,which is one of the reasons for the high mortality rate of HCC.There is a lack of relevant markers to assess the prognosis of patients with hepatocellular carcinoma.Zinc finger CCCH-type containing 13(ZC3H13)is a member of methyltransferase regulators,and existing studies have shown that the expression level of ZC3H13 in HCC patients is controversial.In this study,we aim to investigate the expression and prognostic value of ZC3H13 in HCC patients,and further predict the upstream miRNA of ZC3H13 to clarify the effect of ZC3H13 on the biological behavior of hepatocellular carcinoma cells.Methods: Differential expression analysis of ZC3H13 was conducted based on bioinformatics databases including Oncomine and GEPIA.The expression of ZC3H13 in LX-2 and different hepatoma cells were detected by western blotting.The effects of ZC3H13 on the invasion and migration of hepatocellular carcinoma cells were determined by wound-healing and Transwell assays.The effect of ZC3H13 on the growth of tumor transplantation model in nude mice was detected in vivo.Star Base software was used to predict the upstream miRNA of ZC3H13.The regulation of upstream miRNA on ZC3H13 expression was verified by q PCR and western blotting.The prognostic value of ZC3H13 for HCC patients was evaluated by Kaplan-Meier plotter and the R project.The signaling pathways that ZC3H13 may be involved in the development of HCC was obtained by Linked Omics.Results: 1.The expression of ZC3H13 in hepatocellular carcinoma was significantly reduced by differential expression analysis.2.Low expression of ZC3H13 in hepatocellular carcinoma cell lines were confirmed by western blotting.3.The inhibition effect of ZC3H13 on the invasion and migration of hepatocellular carcinoma cell lines were confirmed by wound-healing and Transwell assays.4.In vivo experiments suggested that ZC3H13 could inhibit the growth of tumor transplantation model in nude mice.5.The expression of ZC3H13 was inhibited by the upstream factor miR-362-3p/miR-425-5p,a result demonstrated by bioinformatics analysis and q PCR and western blotting.6.Survival analysis showed that the lower the expression level of ZC3H13,the worse the prognosis of HCC patients.ZC3H13 can be used to evaluate the prognosis of HCC patients.7.ZC3H13 may be involved in the JAK-STAT signaling pathway and regulates the development of HCC as obtained from Linked Omics database.Conclusion: 1.The low expression of ZC3H13 in hepatocellular carcinoma cells were determined by bioinformatics analysis and western blotting.2.ZC3H13 inhibits the proliferation,invasion and migration of hepatocellular carcinoma cells in vitro and in vivo.3.Upregulation of mir-362-3p/mir-425-5p inhibited ZC3H13,which was verified by realtime quantitative PCR and western blotting.4.ZC3H13 promises to be a novel prognostic marker for HCC patients.