MicroRNA-148a Inhibits Hepatocellular Carcinoma Cell Growth via Epithelial-to-Mesenchymal Transition and PI3K/AKT Signaling Pathways by Targeting Death Receptor-5.

The purpose of this study was to investigate the role of microRNA-148a (miR-148a) in hepatocellular carcinoma (HCC) metastasis and explore its potential mechanism in HCC cells. Expression levels of miR-148a were measured using qRT-PCR in 120 HCC tissue samples and two HCC cell lines. Migration and invasion assays were used to determine the role of miR-148a in HCC cells. Flow cytometry was used to access the effect of miR-148a on cell cycle of HCC cells. Western blot was performed to analyze the effect of miR-148a on epithelial-to-mesenchymal transition (EMT) and PI3K/AKT signaling pathways in HCC cells. Luciferase reporter assay was conducted to explore the downstream targets and biological function of miR-148a in HCC cells. The results showed that level of miR-148a was significantly downregulated in both HCC tissue and plasma samples in HCC patients. A higher level of miR-148a was positively correlated with better survival time and prognosis of HCC patients. Transfection of miR-148a inhibited the proliferation, migration and invasion of HCC cell lines. Transfection of miR-148a arrested HCC cells at S phase and promoted apoptosis of HCC cells. Death receptor-5 (DR-5) was identified as a direct target of miR-148a in HCC cell lines. Western blot and qRT-PCR analyses showed that miR-148a upregulated EMT and downregulated PI3K/AKT signaling pathways in HCC cell lines. In conclusion, data in the current study indicate that miR-148a inhibits HCC cells growth via downregulation of EMT and PI3K/AKT signaling pathways by targeting death receptor. These data suggest that miR-148a may serve as a therapeutic target for HCC cancer therapy in the future.