MicroRNA-421 functions as an oncogenic miRNA in biliary tract cancer through down-regulating farnesoid X receptor expression

MicroRNAs (miRNAs) are involved in the development of most cancers. However, few studies have been conducted to determine their relationship to biliary tract cancer (BTC). Farnesoid X receptor (FXR) has been reported to be a tumor suppressor for hepatocellular carcinoma and breast cancer; but few studies have focused on its correlation with BTC. In this study, we identified miR-421 as a potential regulator of FXR expression. We found that their expression amount was inversely correlated as FXR was aberrantly down-regulated in both primary tumor specimens and cell lines; while miR-421 was significantly up-regulated. Ectopic expression of miR-421 significantly decreased FXR protein concentration in BTC cells and promoted cell proliferation, colony formation and migration in vitro. Furthermore, a decrease in miR-421 expression induced G0/G1 cell cycle arrest. In conclusion, our study identified microRNA-421 functions as an oncomiR in BTC by targeting FXR. This finding may provide a novel therapeutic strategy for treatment of biliary tract cancer.

► We found that farnesoid X receptor is down-regulated while miR-421 is up-regulated in biliary tract cancer.
► Farnesoid X receptor is regulated by miR-421 in biliary tract cancer.
► miR-421 functions as an oncogenic miRNA in biliary tract cancer.
► Down-regulated miR-421 induces cell cycle arrest.