Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

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

Zhi Liu^1,2 , Jianyu Chen^1,2, Lin Mo³, Chuan Lan^1,2, Hui Chen^1,2, Jianshui Li^1,2, Songlin Hou^1,2

¹Department of Hepatobiliary Surgery, Affiliated Hospital of North Sichuan Medical College; ²Institute of Hepatobiliary, Pancreatic and Intestinal Disease, North Sichuan Medical College; ³Department of Pathology, Affiliated Hospital of North Sichuan Medical College, Nanchong City, Sichuan Province 637000, China.

For correspondence:- Zhi Liu Email: ZhiLiuasd@163.com Tel:+868172598137

Accepted: 19 February 2022 Published: 31 March 2022

Citation: Liu Z, Chen J, Mo L, Lan C, Chen H, Li J, et al. Inhibition of miR-182 represses growth of hepatocellular carcinoma cells by targeting SOX11. Trop J Pharm Res 2022; 21(3):471-478 doi: 10.4314/tjpr.v21i3.3

© 2022 The authors.
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Abstract

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 miR-182 repressed proliferation and Bcl-2 expression, but increased protein expression of cleaved caspase-3, 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.

Keywords: microRNA-182, Hepatocellular carcinoma, Apoptosis, SOX11