MicroRNA-455-3p functions as a tumor suppressor by targeting HDAC2 to regulate cell cycle in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of the most common cancers. MicroRNA has been studied more and more deeply and may become a new target for the treatment of HCC. Here, we investigated the role of miR-455-3p in HCC progression. Compared with non-tumor tissues and normal human hepatic cells, miR-455-3p expression was significantly downregulated in HCC tissues and cell lines. And overexpression of miR-455-3p inhibited cell proliferation and migration but promoted cell apoptosis in HCC cell lines HepG2 and Huh7. Mechanism studies displayed that miR-455-3p targeted HDAC2 and negatively regulated HDAC2 expression. Moreover, HDAC2 was highly expressed in HCC tissues and cell lines. Overexpression of HDAC2 reversed the inhibitory effects of miR-455-3p on cell proliferation, migration and cell cycle protein (CDK6 and cyclin D1) expression, and neutralized the promotion effects of miR-455-3p on cell apoptosis and the activation of p53 pathway. Furthermore, a p53 inhibitor Pifithrin-alpha (PFT-alpha) effectively abolished the effects of miR-455-3p on HCC cell behaviors. Additionally, the role of miR-455-3p in tumorigenesis was evaluated by using a mouse xenograft model, and the data showed that miR-455-3p suppressed tumor growth in vivo. In summary, our results suggested that miR-455-3p targeted HDAC2 to inhibit cell proliferation, migration and promote cell apoptosis via the activation of p53 pathway.