Hepatocellular carcinoma (HCC) is notorious for its poor prognosis. Previous studies identified several
N6-methyladenosine (m6A)-related genes that play key roles in the initiation and progression of HCC patients. In particular, the N6-methyladenosine RNA methylation regulator ZC3H13 could be a candidate as a novel
biomarker and therapeutic target for
hepatocellular carcinoma. In HCC, low expression of ZC3H13 was reported, but the molecular reason is unclear. In this study, we performed pan
cancer analysis for ZC3H13 expression and prognosis using The
Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) data and found that ZC3H13 might be a potential tumor suppressor gene in HCC. Subsequently,
miRNAs contributing to ZC3H13 downregulation were identified by a series of in silico analyses, including expression analysis, correlation analysis, and survival analysis. Finally, the miR-362-3p/miR-425-5p-ZC3H13 axis was identified as the most likely upstream
miRNA-related pathway of ZC3H13 in HCC. Additionally, miR-362-3p/miR-425-5p mimic and inhibitor results were detected by quantitative real-time PCR (qPCR) analysis and western blotting. We identified an upstream regulatory mechanism of ZC3H13 in HCC, namely, the miR-362-3p/miR-425-5p-ZC3H13 axis. Moreover, the ZC3H13 level was significantly positively associated with
tumor immune cell infiltration,
biomarkers of immune cells, and immune checkpoint expression. Collectively, our findings elucidated that ncRNA-mediated downregulation of ZC3H13 was correlated with a poor prognosis and
tumor immune infiltration in HCC. In conclusion, this study demonstrates that ZC3H13 is a direct target of miR-362-3p/miR-425-5p in liver
hepatocellular carcinoma (LIHC) that regulates immune modulation in the microenvironment of LIHC.