miR-365 induces hepatocellular carcinoma cell apoptosis through targeting Bcl-2

Abstract

Hepatocellular carcinoma (HCC) is currently ranked as the third leading cause of cancer-related mortality worldwide. microRNAs (miRs) serve important roles in the development and progression of HCC. miR‑365 has been demonstrated to function as a tumor suppressor in several types of cancer, including HCC; however, the mechanisms by which miR-365 regulates HCC apoptosis remains to be elucidated. In the present study, reverse transcription‑quantitative polymerase chain reaction was performed to determine miR‑365 expression levels in HCC and normal liver (LO2) cells. miR‑365 overexpression was induced in SMC7721 cells using a plasmid‑based system, and Cell Counting Kit‑8 and TUNEL assays were performed to detect cell activity and apoptosis following miR‑365 transfection. A luciferase assay was performed to determine the direct target of miR‑365 in apoptosis regulation. Furthermore, a subcutaneously transplanted tumor model was established to evaluate the effects of miR‑365 on tumor growth in vivo. The tumor tissue was used for further proliferation and apoptosis detection. The results of the present study indicated that miR‑365 expression was significantly lower in HCC cells compared with LO2 cells (P<0.01). Transfection of SMC7721 cells with miR‑365 plasmid significantly inhibited cell activity by inducing apoptosis (P<0.01). Luciferase assay indicated that miR‑365 targets B‑cell lymphoma 2 (Bcl‑2) directly and therefore induces the downstream expression of pro‑apoptotic proteins. The SMC7721 primary tumor growth was significantly reduced by miR‑365 transfection (P<0.01). Further investigation demonstrated that the miR‑365 group contained significantly fewer cells that were positive for proliferating cell nuclear antigen (P<0.01) and significantly more apoptotic cells (P<0.01). In conclusion, the results of the present study demonstrated that miR-365 may serve a role in inducing HCC apoptosis via directly targeting Bcl-2. This may provide a novel diagnosis and therapy target for the treatment of patients with HCC.