Hepatic overexpression of miR-200b-3p protects hepatocytes in patients with obstructive cholestasis

Abstract

Objective To investigate the expression of miR-200b-3p and OATP3A1 in the liver of patients with obstructive cholestasis and their protective effects on the hepatocytes. Methods Thirty patients undergoing liver surgeries in our hospital for liver, pancreatic or intestinal malignancies or for calculi in the bile duct or pancreas from January 2012 to June 2016 were enrolled, including 20 with obstructive cholestasis and 10 without cholestasis (control group). The liver functions of the patients were examined and the expression of miR-200b-3p and OATP3A1 in the liver tissues were detected using RT-PCR. The correlations of miR-200b-3p with the liver function and OATP3A1 expression in the patients were analyzed. In the in vitro experiment, HepG2 cells were treated with different cytokines, and the changes in the expression of miR-200b-3p were detected. In both HepG2 and PLC5 cells, the effects of transfection with miR-200b-3p mimic or inhibitor were evaluated on miR-200b-3p and OATP3A1 expression. Results Compared with those in the control patients, the expression of miR-200b-3p and OATP3A1 were significantly increased in the liver tissues of patients with cholestasis (P < 0.05). The expression of miR-200b-3p was positively correlated with OATP3A1 expression (P < 0.05) and the levels of ALP and GGT (P < 0.05), but was negatively correlated with TBA (P < 0.05). In the cell experiment, FGF19 treatment significantly enhanced the expression of miR-200b-3p in HepG2 cells in a time- and dose-dependent manner (P < 0.05). Transfection of HepG2 and PLC5 cells with miR-200b-3p mimic caused significant upregulation of OATP3A1 expression (P < 0.05), while transfection with miR-200b-3p inhibitor significantly downregulated OATP3A1 expression (P < 0.05). Conclusion In patients with obstructive cholestasis, the upregulation of miR-200b-3p enhances OATP3A1 expression in the liver to promote hepatic bile acid efflux and thereby offer protection of the hepatocytes

Keywords

• cholestasis
• mir-200b-3p
• oatp3a1
• fgf19