Inhibition of miR-182 represses growth of hepatocellular carcinoma cells by targeting SOX11

Purpose: To investigate the effect of microRNA-182 (miR-182) on hepatocellular carcinoma (HCC) and its mechanisms of action. Methods: Sixty-five HCC tissues and matched adjacent tissues were obtained, and miR-182 and sex determining region on the Y Chromosome (SRY)-related HMG box 11 (SOX11) expression were quantified using reverse transcription-polymerase chain reaction (RT-PCR). SOX11-positive cells were identified by immunohistochemistry and the correlation between SOX11 and miR-182 expression was analyzed by Spearman correlation analysis. Huh-7 cells were transfected with the miR-182 mimic, the miR-182 inhibitor, and/or si-SOX11, and cell proliferation was measured by cell counting kit-8 (CCK-8) assay. Apoptosis was assessed by flow cytometry. Luciferase reporter assay was used to investigate the putative target gene of miR-182. A xenograft nude mouse model was established by transfection with miR-182 antagomir, while tumor volume and weight were calculated. SOX11, cleaved caspase-3, cleaved poly (ADP ribose) polymerase (PARP), B-cell lymphoma-2 (Bcl-2), and Bcl-2-associated X (Bax) protein levels were analyzed by western blot. Results: MiR-182 expression increased and SOX11 expression was decreased in HCC tissues (p < 0.05). Luciferase reporter assay data confirmed that miR-182 directly targets SOX11. Inhibition of miR182 repressed proliferation and Bcl-2 expression, but increased protein expression of cleaved caspase3, cleaved RAPP, and Bax in Huh-7 cells (p < 0.05). In addition, suppression of SOX11 reversed the effects of miR-182 on cell proliferation and apoptosis. The miR-182 antagomir decreased tumor growth and miR-182 expression but increased SOX11 expression in vivo (p < 0.05). Conclusion: MiR-182 and SOX11 may be novel therapeutic targets for HCC patients.