Abstract
FGF2 and VEGFA are the two most potent angiogenic factors. Here we report that miR-503 can simultaneously down-regulate FGF2 and VEGFA. The expression of miR-503 is repressed in HCC cells and primary tumors due to a potential epigenetic mechanism. Overexpression of miR-503 reduced tumor angiogenesis in vitro and in vivo. We also found that miR-503 expression was down-regulated by hypoxia through HIF1α. These results identify a miRNA that targets both FGF2 and VEGFA in cancers, demonstrate the anti-angiogenesis role of miR-503 in tumorigenesis, and provide a novel mechanism for hypoxia-induced FGF2 and VEGFA through HIF1α-mediated inhibition of miR-503.
Published by Elsevier Ireland Ltd.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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3' Untranslated Regions
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Animals
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Base Sequence
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Carcinoma, Hepatocellular / genetics
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Carcinoma, Hepatocellular / pathology
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DNA Methylation
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Down-Regulation
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Female
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Fibroblast Growth Factors / genetics*
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Gene Expression Regulation, Neoplastic*
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Human Umbilical Vein Endothelial Cells / pathology
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Humans
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Hypoxia-Inducible Factor 1, alpha Subunit / genetics
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Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
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Liver Neoplasms / genetics
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Liver Neoplasms / pathology
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Mice
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Mice, Inbred BALB C
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MicroRNAs / genetics*
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Molecular Sequence Data
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Neovascularization, Pathologic / genetics*
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Neovascularization, Pathologic / pathology
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Promoter Regions, Genetic
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Vascular Endothelial Growth Factor A / genetics*
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Xenograft Model Antitumor Assays
Substances
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3' Untranslated Regions
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FGF20 protein, human
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HIF1A protein, human
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Hypoxia-Inducible Factor 1, alpha Subunit
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MIRN503 microRNA, human
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MicroRNAs
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VEGFA protein, human
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Vascular Endothelial Growth Factor A
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Fibroblast Growth Factors