TGF-β1 Reduces miR-29a Expression to Promote Tumorigenicity and Metastasis of Cholangiocarcinoma by Targeting HDAC4

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-m...

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Bibliographic Details
Published in:PloS one 2015-10, Vol.10 (10), p.e0136703-e0136703
Main Authors: Wang, Huiling, Li, Caixia, Jian, Zhixiang, Ou, Yingliang, Ou, Jinrui
Format: Article
Language:English
Subjects:
Apoptosis
Biotechnology
Blotting, Western
Cancer therapies
Cell cycle
Cell growth
Cell Line, Tumor
Cell Movement - genetics
Cell Movement - physiology
Cell proliferation
Cell Proliferation - genetics
Cell Proliferation - physiology
Cholangiocarcinoma
Cholangiocarcinoma - genetics
Cholangiocarcinoma - metabolism
Cholangiocarcinoma - pathology
Gene expression
Histone Deacetylases - genetics
Histone Deacetylases - metabolism
Hospitals
Humans
Leukemia
Metastases
Metastasis
MicroRNAs
MicroRNAs - genetics
Neoplasm Metastasis - genetics
Pathogenesis
Repressor Proteins - genetics
Repressor Proteins - metabolism
Restoration
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction - drug effects
Surgery
Therapeutic applications
Transforming Growth Factor beta1 - metabolism
Transforming Growth Factor beta1 - pharmacology
Transforming growth factor-b1
Tumor cell lines
Tumorigenicity
Tumors
Wound healing
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Summary: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. TGF-β1/miR-29a/HDAC4 pathway contributes to the pathogenesis of cholangiocarcinoma and our data provide new therapeutic targets for cholangiocarcinoma.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0136703