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MIR-29b Downregulates Canonical Wnt Signaling by Suppressing Coactivators of β-Catenin in Human Colorectal Cancer Cells
Pooja Chandrakant Thacker,
Published in Wiley-Liss Inc.
2014
PMID: 24913975
Volume: 115
   
Issue: 11
Pages: 1974 - 1984
Abstract
The β-catenin/Wnt signaling pathway is activated in many cancers and its constitutive activation has a central role in colorectal cancer pathogenesis. Recent studies have highlighted the role of microRNAs as novel regulators of gene expression including that of signaling intermediates from the Wnt signaling pathway. The purpose of our study was to determine the role of miR-29b in the regulation of Wnt signaling in human colorectal cancer cells. TOPFlash/FOPFlash reporter assays, gene expression studies by quantitative RT-PCR and western blot analysis were used to study the effect of ectopic expression of miR-29b on canonical Wnt signaling. miR-29b antagonized transactivation of β-catenin target genes by downregulating coactivators of β-catenin (TCF7L2, Snail, and BCL9L) in SW480 cells. miR-29b targeted the 3′UTR of BCL9L and decreased its expression with a consequent decrease in nuclear translocation of β-catenin. Ectopic expression of miR-29b inhibited anchorage independent cell growth, promoted reversal of epithelial to mesenchymal transition and reduced the ability of conditioned medium from SW480 cells to induce in vitro tube formation in endothelial cells. These results have unraveled a novel role of miR-29b in Wnt signaling in human colorectal cancer cells with implications in the treatment of colorectal cancer. J. Cell. Biochem. 115: 1974-1984, 2014. © 2014 Wiley Periodicals, Inc.
About the journal
JournalData powered by TypesetJournal of Cellular Biochemistry
PublisherData powered by TypesetWiley-Liss Inc.
ISSN07302312
Open AccessNo
Concepts (50)
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    Beta catenin
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    MICRORNA 29B
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    Protein p53
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    TRANSCRIPTION FACTOR 7 LIKE 2
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    TRANSCRIPTION FACTOR SNAIL
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    UVOMORULIN
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    BCL9L PROTEIN, HUMAN
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    CTNNB1 PROTEIN, HUMAN
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    Dna binding protein
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    Microrna
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    MIRN29 MICRORNA, HUMAN
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    SNAIL FAMILY TRANSCRIPTION FACTORS
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    TCF7L2 PROTEIN, HUMAN
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    Transcription factor
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    TRANSCRIPTION FACTOR 7 LIKE 2
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    3' UNTRANSLATED REGION
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    Article
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    Cell growth
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    Colorectal cancer
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    Down regulation
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    ECTOPIC EXPRESSION
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    Endothelium cell
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    Epithelial mesenchymal transition
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    Gene expression
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    Human
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    Human cell
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    Priority journal
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    Reverse transcription polymerase chain reaction
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    TRANSACTIVATION
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    Western blotting
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    WNT SIGNALING PATHWAY
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    COLORECTAL TUMOR
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    Gene expression regulation
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    Genetics
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    HCT116 CELL LINE
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    Hek293 cell line
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    Metabolism
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    Tumor cell line
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    Cell line, tumor
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    COLORECTAL NEOPLASMS
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    Dna-binding proteins
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    Epithelial-mesenchymal transition
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    GENE EXPRESSION REGULATION, NEOPLASTIC
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    HCT116 CELLS
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    Hek293 cells
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    Humans
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    Micrornas
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    TRANSCRIPTION FACTOR 7-LIKE 2 PROTEIN
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    Transcription factors
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    WNT SIGNALING PATHWAY