title: Expression profile of microRNA-200 family in cholangiocarcinoma arising from choledochal cyst.
abstract: OBJECTIVE
  The risk of cholangiocarcinoma (cCC) arising from choledochal cyst (CC-CC) is imminent, if the latter not treated appropriately in time. Epithelial-to-mesenchymal transition (EMT) is considered a critical step for various solid cancers, which is regulated by the microRNA-200 (miR-200) family. The aim of this study was to assess the role of miR-200 family in the pathogenesis of CC-CC.
  
  
  METHODS
  Sixteen patients with CC-CC were enrolled and 254 patients with conventional cCC served as clinicopathologic controls. Fifty-four cCC were selected to compare the miR-200 family expression and immunohistochemical characteristics. Gain-and loss-of-function studies of miR-200 family were conducted using the cCC cell lines.
  
  
  RESULTS
  CC-CC were younger (P < 0.01), more female- predominated (P < 0.01), and rarely associated with lithiasis (P < 0.01) compared with those of cCC. miR-200 family was down-regulated in CC-CC, while miR-200 family was paradoxically up-regulated in cCC (P < 0.01). CC-CC exhibited overt overexpression of mesenchymal markers including ZEB1, Twist, Snail, and vimentin as well an aberrant E-cadherin expression in comparison with cCC. In vitro migration assay showed that cCC cells bearing lower miR-200 s levels exhibited stronger migration ability. Invasive ability of cCC cells was increased after miR-200 s knockdown, accompanied by up-regulation of mesenchymal markers.
  
  
  CONCLUSIONS
  CC-CC was characterized by distinct demographics, precipitating factors, and down-regulation of miR-200 family, compared with those of cCC. The pathogenesis of CC-CC might partly link to the silencing of miR-200 family, acting via ZEB1-directed EMT activation.
authors.affiliation: Department of Surgery, Chang Gung Memorial Hospital, Chang Gung University Medical College, LinKou, Taiwan.
authors.forename: Chia-Hui
authors.initials: CH
authors.lastname: Chu
authors.affiliation: Department of Medical Oncology, Chang Gung Memorial Hospital, Chang Gung University Medical College, LinKou, Taiwan.|Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Wenchi
authors.initials: W
authors.lastname: Chou
authors.affiliation: Department of Surgery, Chang Gung Memorial Hospital, Chang Gung University Medical College, LinKou, Taiwan.
authors.forename: Frank
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Surgery, Chang Gung Memorial Hospital, Chang Gung University Medical College, LinKou, Taiwan.
authors.forename: Chun-Nan
authors.initials: CN
authors.lastname: Yeh
authors.affiliation: Department of Pathology, Chang Gung Memorial Hospital, Chang Gung University Medical College, LinKou, Taiwan.
authors.forename: Tse-Ching
authors.initials: TC
authors.lastname: Chen
authors.affiliation: Department of Surgery, Chang Gung Memorial Hospital, Chang Gung University Medical College, LinKou, Taiwan.|Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Ta-Sen
authors.initials: TS
authors.lastname: Yeh
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD; D001650:Bile Duct Neoplasms / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D014408:Biomarkers, Tumor / Q000235:genetics*; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D002465:Cell Movement; D018281:Cholangiocarcinoma / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D015529:Choledochal Cyst / Q000150:complications* / Q000175:diagnosis; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D000071250:Snail Family Transcription Factors / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D000071416:Twist Transcription Factors / Q000235:genetics / Q000378:metabolism; D014746:Vimentin / Q000235:genetics / Q000378:metabolism; D000071799:Zinc Finger E-box-Binding Homeobox 1 / Q000235:genetics / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D014408:Biomarkers, Tumor; C513384:CDH1 protein, human; D015820:Cadherins; D035683:MicroRNAs; D000071250:Snail Family Transcription Factors; D000071416:Twist Transcription Factors; D014746:Vimentin; C486307:ZEB1 protein, human; D000071799:Zinc Finger E-box-Binding Homeobox 1
keywords: carcinogenesis and metastasis; gastroenterology; gastroenterology, biliary: congenital disorders; gastroenterology, biliary: neoplasms