title: miR-204 inhibits epithelial to mesenchymal transition by targeting slug in intrahepatic cholangiocarcinoma cells.
abstract: OBJECTIVE
  MicroRNAs (miRNAs) play critical roles during carcinogenesis and cancer progression. Down-regulation of miR-204 has been frequently observed in various cancers. In this study, we investigated the roles and mechanisms of miR-204 in human intrahepatic cholangiocarcinoma (ICC).
  
  
  METHODS
  The relative expression of miR-204 in ICC tissues and cell lines was monitored by qRT-PCR. Effects of miR-204 were studied in human ICC cell lines HuH28 and HuCCT1, and cells were analyzed for proliferation, migration and invasion. Expression levels of miR-204 target gene Slug and EMT markers (E-cadherin and vimentin) in ICC cell lines and tissues were measured by qRT-PCR, western blotting and immunofluorescence.
  
  
  RESULTS
  miR-204 was frequently downregulated in human ICC, and the low-level expression of miR-204 was significantly associated with lymph node metastasis. Overexpression of miR-204 dramatically suppressed ICC cell migration and invasion, as well as the epithelial-mesenchymal transition process (EMT). Slug was identified as a direct target of miR-204, and its downregulation by miR-204 in HuH28 cells reversed EMT, as shown by the increased expression of the epithelial marker E-cadherin and decreased expression of the mesenchymal marker vimentin.
  
  
  CONCLUSIONS
  These findings suggest that miR-204 plays negative roles in the invasive and/or metastatic potential of ICC, and that its suppressive effects are mediated by repressing Slug expression.
authors.affiliation: The Second Department of Biliary Tract Surgery, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China.
authors.forename: Ying-he
authors.initials: YH
authors.lastname: Qiu
authors.forename: Yong-peng
authors.initials: YP
authors.lastname: Wei
authors.forename: Ning-jia
authors.initials: NJ
authors.lastname: Shen
authors.forename: Zhou-chong
authors.initials: ZC
authors.lastname: Wang
authors.forename: Tong
authors.initials: T
authors.lastname: Kan
authors.forename: Wen-long
authors.initials: WL
authors.lastname: Yu
authors.forename: Bin
authors.initials: B
authors.lastname: Yi
authors.forename: Yong-jie
authors.initials: YJ
authors.lastname: Zhang
mesh_terms: D001650:Bile Duct Neoplasms; D001653:Bile Ducts, Intrahepatic; D015820:Cadherins / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D018281:Cholangiocarcinoma / Q000235:genetics* / Q000473:pathology*; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology*; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics*; D014746:Vimentin / Q000235:genetics
chemical_list: D015820:Cadherins; C549404:MIRN204 microRNA, human; D035683:MicroRNAs; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D014746:Vimentin