Expression profile of MicroRNA-200 family in hepatocellular carcinoma with bile duct tumor thrombus

Ta Sen Yeh*, Frank Wang, Tse Ching Chen, Chun Nan Yeh, Ming Chin Yu, Yi Yin Jan, Miin Fu Chen

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

39 Scopus citations


OBJECTIVE:: The aim of this study was to assess the role of the miR-200 family in the pathogenesis of hepatocellular carcinoma with bile duct tumor thrombus (HCC-BDTT). BACKGROUND:: Hepatocellular carcinoma with bile duct tumor thrombus is a challenging condition because of its rarity and dismal prognosis. Epithelial-to-mesenchymal transition (EMT) is considered a critical step in the progression and metastasis of HCC and is regulated by the microRNA-200 (miR-200) family. METHODS:: Thirty patients with HCC-BDTT were enrolled and 1240 patients with conventional HCC (cHCC) served as clinicopathologic controls. Sixty age-And sex-matched cHCC patients were selected to compare the miR-200 family expression profile and immunohistochemical characteristics. Gain-And loss-of-function studies of the miR-200 family were conducted using the hepatoma cell lines. RESULTS:: Although the mean size of HCC-BDTT was smaller than that of cHCC, the former had a higher incidence of vascular invasion and a poorer long-term survival. The expressions of miR-200c and miR-141 were downregulated in HCC-BDTT (4.5-And 4.8-fold decrease, respectively). Downregulation of both miR-200c and miR-141 independently predicted disease-free survival. The HCC-BDTT, but not cHCC, exhibited overexpression of ZEB1, Twist, transforming growth factor-β receptor type II, and vimentin, and aberrant E-cadherin expression, indicating EMT. The HCC-BDTT demonstrated increased expression in IL-6 and stemness factor Bmi1, but reduced level of metastasis-suppressive protein, insulin-like growth factor-binding protein 4. The invasive ability of the highly aggressive Mahlavu cell was attenuated by pre-miR-200c+141, whereas the invasive ability of the less aggressive Huh7 cell was enhanced by anti-miR-200c+141. CONCLUSIONS:: Simultaneous silencing of miR-200c and miR-141 was likely to be responsible for the development of HCC-BDTT via ZEB1-directed EMT activation and Sec23a-mediated secretome.

Original languageEnglish
Pages (from-to)346-354
Number of pages9
JournalAnnals of Surgery
Issue number2
StatePublished - 02 2014
Externally publishedYes


  • epithelial-to-mesenchymal transition
  • hepatocellular carcinoma with bile duct tumor thrombosis
  • microRNA-200 family


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