title: TGF-β1 Reduces miR-29a Expression to Promote Tumorigenicity and Metastasis of Cholangiocarcinoma by Targeting HDAC4.
abstract: Transforming growth factor β1 (TGF-β1) and miRNAs play important roles in cholangiocarcinoma progression. In this study, miR-29a level was found significantly decreased in both cholangiocarcinoma tissues and tumor cell lines. TGF-β1 reduced miR-29a expression in tumor cell lines. Furthermore, anti-miR-29a reduced the proliferation and metastasis capacity of cholangiocarcinoma cell lines in vitro, overexpression of miR-29a counteracted TGF-β1-mediated cell growth and metastasis. Subsequent investigation identified HDAC4 is a direct target of miR-29a. In addition, restoration of HDAC4 attenuated miR-29a-mediated inhibition of cell proliferation and metastasis.
  
  
  CONCLUSIONS
  TGF-β1/miR-29a/HDAC4 pathway contributes to the pathogenesis of cholangiocarcinoma and our data provide new therapeutic targets for cholangiocarcinoma.
authors.affiliation: General Surgery Department of Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, China.
authors.forename: Huiling
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Rheumatology, The First Affiliated Hospital/School of Clinical Medicine of Guangdong Pharmaceutical University, Guangzhou, Guangdong 510080, China.
authors.forename: Caixia
authors.initials: C
authors.lastname: Li
authors.affiliation: General Surgery Department of Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, China.
authors.forename: Zhixiang
authors.initials: Z
authors.lastname: Jian
authors.affiliation: General Surgery Department of Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, China.
authors.forename: Yingliang
authors.initials: Y
authors.lastname: Ou
authors.affiliation: General Surgery Department of Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, China.
authors.forename: Jinrui
authors.initials: J
authors.lastname: Ou
mesh_terms: D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics / Q000502:physiology; D049109:Cell Proliferation / Q000235:genetics / Q000502:physiology; D018281:Cholangiocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D009362:Neoplasm Metastasis / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D053773:Transforming Growth Factor beta1 / Q000378:metabolism* / Q000494:pharmacology*
chemical_list: C532045:MIRN29a microRNA, human; D035683:MicroRNAs; D012097:Repressor Proteins; D053773:Transforming Growth Factor beta1; C400300:HDAC4 protein, human; D006655:Histone Deacetylases