MicroRNA-185 modulates CYP7A1 mediated bile acid metabolism through posttranscriptionally and posttranslationally regulation of FoxO1. MicroRNA-185 modulates CYP7A1 mediated bile acid metabolism through posttranscriptionally and posttranslationally regulation of FoxO1

Cholesterol 7alpha-hydroxylase (CYP7A1) is the rate limiting enzyme of bile acid biosynthetic pathway to convert cholesterol to bile acids, which is a major output pathway for cholesterol catabolism. In this study, we aimed to assess the potential regulatory mechanisms of microRNA-185 (miR-185) involved in cholesterol and bile acid homeostasis. This study provides convincing evidences about the critical role of miR-185 in FoxO1 modulation at both posttranscriptional and posttranslational levels, which account for the effects on CYP7A1 gene and its mediated cholesterol-bile acid metabolism. These results suggest an important role of miR-185 as a novel atherosclerosis-protective target for drug discovery. Overall design: Eight-week-old male ApoE KO mice fed a high-fat diet (HFD) were injected with lentiviruses encoding antisense miR-185 (miR-185-inh). Microarrays were applied to profile miR-185-regulated genes involved in bile acid metabolism.