Abnormal expression and mechanism of miR-330-3p/BTG1 axis in hepatocellular carcinoma.

Abstract

Increasing evidence has suggested that microRNAs (miRNAs) played critical roles in cancer development by acting as a tumor suppressor or tumor-promoting genes. However, the role of microRNA-330-3p (miR-330-3p) in hepatocellular carcinoma (HCC) is still unknown. This study aimed to investigate the expression and role of miR-330-3p in hepatocarcinogenesis. A total of 30 human hepatocellular carcinoma tissues and adjacent normal tissues were obtained from 30 hepatocellular carcinoma patients. Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) assay was carried out to measure the expression of miR-330-3p in HCC tissues and cell lines. The relation between B-cell translocation gene 1 (BTG1) and miR-330-3p was predicted by TargetScan and confirmed by dual-luciferase reporter assay. Cell Counting Kit-8 (CCK-8), flow cytometry analysis, and transwell assay were used to determine cell viability, apoptosis, cell migration, and invasion, respectively. In addition, the mRNA and protein expression of Cyclin D1, Bcl-2, Bax, and matrix metalloproteinase (MMP)9 were detected using qRT-PCR and Western blotting. We found that miR-330-3p expression was up-regulated in HCC tissues and cell lines. BTG1 was a direct target of miR-330-3p and it was down-regulated in HCC tissues and cell lines. Moreover, down-regulation of miR-330-3p suppressed HCCLM3 cell viability, migration, invasion, and enhanced cell apoptosis, while the tumor-suppressive effects were reversed by BTG1-siRNA. In addition, miR-330-3p inhibitor decreased the expression of Cyclin D1, Bcl-2, and MMP9 while enhanced the expression of Bax. Meanwhile, BTG1-siRNA led to the opposite effects. The data suggested that miR-330-3p acted as a tumor gene in HCC by targeting BTG1 and it might be a potential therapeutic target for the HCC treatment.