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.
MeSH terms
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Blotting, Western
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Cell Line, Tumor
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Cell Movement / genetics
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Cell Movement / physiology
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Cell Proliferation / genetics
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Cell Proliferation / physiology
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Cholangiocarcinoma / genetics
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Cholangiocarcinoma / metabolism*
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Cholangiocarcinoma / pathology
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Histone Deacetylases / genetics
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Histone Deacetylases / metabolism*
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Humans
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MicroRNAs / genetics*
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Neoplasm Metastasis / genetics
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Repressor Proteins / genetics
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Repressor Proteins / metabolism*
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Reverse Transcriptase Polymerase Chain Reaction
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Signal Transduction / drug effects
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Transforming Growth Factor beta1 / metabolism*
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Transforming Growth Factor beta1 / pharmacology*
Substances
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MIRN29a microRNA, human
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MicroRNAs
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Repressor Proteins
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Transforming Growth Factor beta1
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HDAC4 protein, human
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Histone Deacetylases
Grants and funding
The authors received no specific funding for this work.