Identification and validation of the N6-methyladenosine RNA methylation regulator ZC3H13 as a novel prognostic marker and potential target for hepatocellular carcinoma

Abstract

N6-methyladenosine (m6A) RNA methylation has been implicated in various malignancies. This study aimed to identify prognostic signature based on m6A methylation regulators for hepatocellular carcinoma (HCC) and provide candidate targets for HCC treatment. In this study, the expression levels, prognostic values, correlation with tumor grades and genetic variations of m6A-related genes in HCC were evaluated using bioinformatics analyses. Interestingly, the results show that methyltransferase zinc finger CCCH-type containing 13 (ZC3H13) was expressed at a significantly low level in HCC. Survival outcome analysis suggested that significant correlations existed between ZC3H13 downregulation and poor overall survival (OS) and poor recurrence-free survival (RFS) in HCC patients. Therefore, ZC3H13 was chosen for further experimental validation. The expression of ZC3H13 in HCC cell lines was investigated by western blotting. Knockdown of ZC3H13 significantly enhanced the migration and invasion of HCC cells, as demonstrated by wound healing and transwell assays. Moreover, upregulating ZC3H13 repressed the growth of xenograft tumors in vivo. Functional and pathway enrichment analyses indicated that ZC3H13 might be involved in transcriptional dysregulation or the JAK-STAT signaling pathway in cancer. Additionally, ZC3H13 expression was significantly correlated with lymphocytes and immunomodulators. Therefore, ZC3H13 is a promising candidate as a novel biomarker and therapeutic target for HCC.