Expression profile of microRNA-200 family in cholangiocarcinoma arising from choledochal cyst.
BACKGROUND AND AIM
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.
['Chu|Chia-Hui|CH|', 'Chou|Wenchi|W|', 'Wang|Frank|F|', 'Yeh|Chun-Nan|CN|', 'Chen|Tse-Ching|TC|', 'Yeh|Ta-Sen|TS|']
D000328:Adult D000368:Aged D015703:Antigens, CD D001650:Bile Duct Neoplasms D014408:Biomarkers, Tumor D015820:Cadherins D016022:Case-Control Studies D045744:Cell Line, Tumor D002465:Cell Movement D018281:Cholangiocarcinoma D015529:Choledochal Cyst D005260:Female D015972:Gene Expression Regulation, Neoplastic D006801:Humans D008297:Male D035683:MicroRNAs D008875:Middle Aged D009361:Neoplasm Invasiveness D000071250:Snail Family Transcription Factors D013997:Time Factors D014162:Transfection D000071416:Twist Transcription Factors D014746:Vimentin D000071799:Zinc Finger E-box-Binding Homeobox 1
carcinogenesis and metastasis gastroenterology gastroenterology, biliary: congenital disorders gastroenterology, biliary: neoplasms