Curcumin Suppresses Cell Proliferation, Migration, and Invasion Through Modulating miR-21-5p/ SOX6 Axis in Hepatocellular Carcinoma

Cancer Biother Radiopharm. 2020 Aug 4. doi: 10.1089/cbr.2020.3734. Online ahead of print.

Abstract

Background: Curcumin is the major component of turmeric, which has an anticancer property in multiple cancers, including hepatocellular carcinoma (HCC). However, the mechanisms are still largely unclear. This research aims to assess the pharmacological function of curcumin and explore the potential microRNA (miRNA)-mRNA regulatory mechanism in curcumin-mediated HCC progression. Materials and Methods: Hep3B and Huh-7 cells were used for in vitro experiments. Cells were exposed to various doses of curcumin, and transfection was conducted using Lipofectamine 2000. Cell proliferation, migration, and invasion were examined using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide or transwell assay. The abundances of miR-21-5p and gender-determining region Y-related high-mobility group box 6 (SOX6) were examined using quantitative real-time polymerase chain reaction or Western blot. The relationship between miR-21-5p and SOX6 was analyzed through luciferase reporter analysis. Results: Curcumin repressed HCC cell proliferation, migration, and invasion. miR-21-5p level was decreased in curcumin-treated cells, and miR-21-5p overexpression reversed curcumin-mediated inhibition of HCC progression. SOX6 was targeted through miR-21-5p, and SOX6 restoration attenuated miR-21-5p-induced promotion of HCC progression. Moreover, curcumin exposure increased SOX6 expression through regulating miR-21-5p, and knockdown of SOX6 overturned curcumin-modulated suppression of HCC progression. Conclusions: Curcumin repressed proliferation, migration, and invasion of HCC cells by regulating miR-21-5p and SOX6, indicating the promisingly pharmacological effect of curcumin in HCC.

Keywords: SOX6; curcumin; hepatocellular carcinoma; miR-21-5p.