Abstract
Persistent activation of Wnt/β-catenin signaling plays crucial roles in the development of human cancers, including hepatocellular carcinoma (HCC). Here, we performed a MicroRNA-based genetic screen, which revealed a novel diversion in β-catenin signaling triggered by MicroRNA-153 (miR-153). Overexpression of miR-153 was able to promote β-catenin transcriptional activity, leading to cell-cycle progression, proliferation and colony formation of HCC cells. Additionally, systemic administration of miR-153 antigomir suppressed hepatocellular carcinogenesis in a murine liver cancer model. At the molecular level, we found that miR-153 inhibited protein level of WWOX, a tumor suppressor and inhibitor of β-catenin signaling, through targeting its 3'-untranslated region. Therefore, our study highlights the importance of MicroRNA-153/WWOX/β-catenin regulatory axis in the HCC tumorigenesis.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Base Sequence
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Carcinoma, Hepatocellular / genetics*
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Carcinoma, Hepatocellular / metabolism
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Cell Growth Processes / genetics
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Cell Line, Tumor
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Hep G2 Cells
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Humans
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Liver Neoplasms / genetics*
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Liver Neoplasms / metabolism
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Male
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Mice
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Mice, Inbred BALB C
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MicroRNAs / genetics*
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MicroRNAs / metabolism
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Oxidoreductases / antagonists & inhibitors
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Oxidoreductases / genetics*
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Oxidoreductases / metabolism
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Transfection
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Tumor Suppressor Proteins / antagonists & inhibitors
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Tumor Suppressor Proteins / genetics*
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Tumor Suppressor Proteins / metabolism
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WW Domain-Containing Oxidoreductase
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Wnt Signaling Pathway*
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beta Catenin / genetics
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beta Catenin / metabolism*
Substances
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CTNNB1 protein, human
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MIRN153 microRNA, human
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MicroRNAs
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Tumor Suppressor Proteins
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beta Catenin
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Oxidoreductases
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WW Domain-Containing Oxidoreductase
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WWOX protein, human