MiRNA-200b-3p represses LRH-1 expression and is associated with reduced serum bile acid in human obstructive cholestasis

Background: MicroRNAs are closely associated with liver diseases including cholestasis, but the roles of miR-200 family in cholestasis has not been determined. Liver receptor homolog-1 (LRH-1/NR5A2) plays an important role in maintaining bile acid homeostasis by regulating some genes, including CYP7A1 and CYP8B1, but the mechanistic details remain to be elucidated in human cholestasis. Methods The mRNA and or protein expressions of miR-200b-3p, LRH-1, CYP7A1 and CYP8B1 in human liver tissues (11 controls and 24 cholestasis) were analyzed using RT-PCR or Western blot. HepG2 cells was transfected with miR-200b-3p mimic to determine gene expressions. We used luciferase gene reporter assay to identify the potential response element of miR-200b-3p in LRH-1 gene. Results MiR-200b-3p was increased for about 2 folds in cholestatic liver tissues, which were divided into low and high expression group. Serum TBA was negatively correlated with miR-200b-3p in miR-200b-3p high expression group. Levels of LRH-1, CYP8B1 and CYP7A1 were decreased, LRH-1 and CYP8B1 were negatively correlated with miR-200b-3p in miR-200b-3p high expression group. MiR-200b-3p mimic was transfected into HepG2 cells, the levels of LRH-1, CYP7A1 and CYP8B1 were significantly repressed by 45%-55%. Bioinformatics analysis revealed the potential binding site of LRH-1 and miR-200b-3p and luciferase reporter gene assay showed that miR-200b-3p might directly bind with LRH-1. Conclusions Our findings indicate that miR-200b-3p represses liver LRH-1, which in turn decreases bile acid synthesis, suggesting that miR-200b-3p may be a potential therapeutic target for cholestasis.