miRNA-518a-3p Inhibits Hepatocarcinogenesis by Down-Regulating ZNF281

Abstract

Background: Emerging evidence has indicated that microRNAs (miRNAs) play a significant role in multiple biological processes, including controlling the cell cycle, apoptosis, autophagy, and metabolic reprogramming. Among them, microRNA (miRNA)-518a-3p has been revealed to display a notably key function during the development of many cancer types, including colorectal cancer, breast cancer, and squamous cell carcinoma. However, its functions and molecular mechanisms during hepatocellular carcinoma (HCC) progression remain unclear. In this study, we aim to elucidate the specific biological processes and mechanisms of miRNA-518a-3p affecting HCC, so as to provide reference for finding new therapeutic targets. Methods: Molecular and cell biology experiments were used to demonstrate the biological functions and molecular mechanisms of miRNA-518a-3p in HCC. Quantitative reverse transcription PCR (RT-qPCR) detected the miRNA-518a-3p expression level in HCC tumor tissues, and its related prognostic effects were also investigated. Furthermore, its functions during HCC progression were investigated by Cell Counting Kit-8 (CCK-8) experiment, transwell assay in two HCC cell lines. Moreover, its potential mechanisms were analyzed by bioinformatic analysis, RT-qPCR, western blotting, a luciferase reporter assay, and rescue experiments. Results: Downregulation of miRNA-518a-3p was found in HCC tumor tissues and correlated with an awful overall survival. Gain and loss of function analyses displayed miRNA-518a-3p repressed HCC cells proliferation, migration, and invasion. Bioinformatic analysis and luciferase reporter assays have shown that Zinc finger protein 281 (ZNF281), upregulated in HCC tumor tissues, was negatively regulated by miRNA-518a-3p. Moreover, rescue experiments demonstrated that the suppression of HCC progression by miRNA-518a-3p was mediated by ZNF281. Conclusions: Our study indicated that miRNA-518a-3p inhibited hepatocarcinogenesis by suppressing ZNF281 expression, indicating that miRNA-518a-3p is a promising therapeutic approach targeting the treatment of HCC.