Activation of miR-101-3p/EZH2 pathway enhances sorafenib sensitivity of HepG2 cells

Abstract

Objective To investigate the effect of activating the miR-101-3p/EZH2 pathway on sorafenib sensitivity of HepG2 cells. Methods HepG2 cells treated with sorafenib (10 μmol/L) for 24 h were examined for protein expression of enhancer of zeste homolog 2 (EZH2) using Western blotting and for mRNA expression of EZH2 and miR-101-3p using RT-qPCR. The interaction between miR-101-3p and EZH2 mRNA was analyzed through informatics analysis and verified using dual luciferase reporter assay. HepG2 cells were transfected with miR-101-3p mimic or treated with the EZH2 inhibitor EPZ-6438 followed by treatment with sorafenib for 24 h, and the change in cell proliferation was assessed using CCK-8 assay. Results Sorafenib obviously decreased the expression of miR-101-3p in HepG2 cells (P < 0.05). Informatics analysis showed that miR-101-3p could bind to the 3'-UTR of EZH2 mRNA, and transfection with miR-101-3p significantly inhibited the expression of EZH2 in HepG2 cells (P < 0.05). Sorafenib treatment significantly increased the expression of EZH2 in HepG2 cells (P < 0.05). Both miR-101-3p over-expression and EPZ-6438 treatment resulted in significantly increased sorafenib sensitivity of HepG2 cells (P < 0.05). Conclusion Activation of the miR-101-3p/EZH2 pathway can enhance sorafenib sensitivity of HepG2 cells.

Keywords

• microrna
• sorafenib
• drug resistance
• hepatoma
• enhancer of zeste homolog 2