title: MicroRNA-421 functions as an oncogenic miRNA in biliary tract cancer through down-regulating farnesoid X receptor expression.
abstract: 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 G(0)/G(1) 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.
authors.affiliation: Department of Hepatopancreatobiliary Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China.
authors.forename: Xiang-yu
authors.initials: XY
authors.lastname: Zhong
authors.forename: Jian-hua
authors.initials: JH
authors.lastname: Yu
authors.forename: Wei-guang
authors.initials: WG
authors.lastname: Zhang
authors.forename: Zhi-dong
authors.initials: ZD
authors.lastname: Wang
authors.forename: Qin
authors.initials: Q
authors.lastname: Dong
authors.forename: Sheng
authors.initials: S
authors.lastname: Tai
authors.forename: Yun-fu
authors.initials: YF
authors.lastname: Cui
authors.forename: Hui
authors.initials: H
authors.lastname: Li
mesh_terms: D001661:Biliary Tract Neoplasms / Q000235:genetics*; D059447:Cell Cycle Checkpoints; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018281:Cholangiocarcinoma / Q000235:genetics*; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans