title: Down-regulation of miR-214 contributes to intrahepatic cholangiocarcinoma metastasis by targeting Twist.
abstract: miRNAs play an important role in many human diseases, including cancer metastasis. However, the mechanisms by which miRNAs regulate intrahepatic cholangiocarcinoma metastasis remain poorly understood. In the present study, we assayed the expression level of miR-214 in intrahepatic cholangiocarcinoma tissues by real-time PCR, and defined the target gene and biological function by luciferase reporter assay and Western blot analysis. We found that the miR-214 levels were remarkably decreased in metastatic intrahepatic cholangiocarcinoma tissues compared to non-metastatic tissues. Inhibition of miR-214 levels by its inhibitor promoted metastasis of human intrahepatic cholangiocarcinoma cell. We further demonstrated that down-regulation of miR-214 increased the transcript levels of the epithelial-mesenchymal transition-associated gene Twist, and then decreased E-cadherin levels. We confirmed that down-regulation of miR-214 promoted the epithelial-mesenchymal transition by directly targeting the Twist gene. These results suggest an important role for miR-214 in regulating metastasis of intrahepatic cholangiocarcinoma, and potential application of miR-214 in intrahepatic cholangiocarcinoma therapy.
authors.affiliation: Department of Biliary Truct Surgery I, Eastern Hepatobiliary Hospital, Secondary Military Medicine University, Shanghai, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Li
authors.forename: Qingqi
authors.initials: Q
authors.lastname: Han
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhu
authors.forename: Yong
authors.initials: Y
authors.lastname: Yu
authors.forename: Jinghan
authors.initials: J
authors.lastname: Wang
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Jiang
mesh_terms: D001650:Bile Duct Neoplasms; D001653:Bile Ducts, Intrahepatic; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement; D018281:Cholangiocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000556:secondary*; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000556:secondary*; D008156:Luciferases / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051879:Twist-Related Protein 1 / Q000235:genetics / Q000378:metabolism*
chemical_list: C547397:MIRN214 microRNA, human; D035683:MicroRNAs; D009687:Nuclear Proteins; D012333:RNA, Messenger; C103173:TWIST1 protein, human; D051879:Twist-Related Protein 1; D008156:Luciferases