Abstract
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.
Highlights
Hepatocellular carcinoma (HCC) is the third most common cause of cancer death worldwide [1]
The results showed that zinc finger CCCH-type containing 13 (ZC3H13) expression was significantly increased in patients with DLBC, ESCA, LAML, PAAD, SKCM, STAD and THYM (Figure 1B)
In liver hepatocellular carcinoma (LIHC), ZC3H13 was significantly decreased (Figure 1C). Both database results confirmed that ZC3H13 is downregulated in HCC, suggesting that abnormal ZC3H13 may drive the carcinogenesis of HCC
Summary
Hepatocellular carcinoma (HCC) is the third most common cause of cancer death worldwide [1]. The difficulty in diagnosing hepatocellular carcinoma at an early stage is due to the lack of typical clinical symptoms in patients www.aging-us.com with HCC. With the advancement of medicine, considerable progress has been made in the diagnosis, treatment and prognosis, but the prognosis of HCC patients remains unsatisfactory, and more than 700,000 people still die each year [4]. Because of this high lethality rate and high risk of recurrence in postoperative patients, dynamic surveillance of hepatocellular carcinoma is necessary [5]. Identifying promising HCC prognostic biomarkers and developing effective therapeutic targets are the main tasks of current studies
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