miR199a represses the proliferation of hepatocellular carcinoma cells by targeting SGK3 through Akt/mTOR pathway

Abstract

Abstract Purpose Previous studies have suggested that some microRNAs (miRNAs) play a vital role in carcinogenesis and progression of hepatocellular carcinoma (HCC). As one of these newly found miRNAs, miR-199a-3p (miR199a), has been shown to be highly involved in the regulation of HCC growth. However, the mechanism underlying miR199a regulation in HCC remains unclear. Methods In this study, the evaluation of miR199a expression in HCC cells (HCCs) and tissues was evaluated by RT-qPCR. Bioinformatics analysis and luciferase reporter assay were performed to prove the regulation effect of miR199a on SGK3. CCK-8 assay was performed to assess the proliferation of HCCs (HepG2 and HuH7) after transfection. Subsequently, the biological function of miR199a/SGK3 axis in HCCs was investigated. Results Herein, we found that miR199a is usually underexpressed in the HCC tissue and cell lines (HepG2 and HuH7) compared with their corresponding control. The expression pattern of SGK3, as a direct target of miR199a, was opposite that of miR199a. shRNA-mediated silencing of SGK3 decreased the proliferation of HCC cells (HCCs) in vitro; however, these phenotypes were promoted by miR199a mimics. Mechanistically, miR199a inhibited the proliferation of HCCs through the downregulation Akt/mTOR signalling by targeting SGK3. Conclusion our findings demonstrated an important role for SGK3 as a miR199a target and a mediator of the Akt/mTOR signaling pathway. These findings highlight the miR199a/SGK3 axis as a potential therapeutic target for managing HCC.