Journal of Cellular Biochemistry

MiR-29b Downregulates Canonical Wnt Signaling by Suppressing Coactivators of β-Catenin in Human Colorectal Cancer Cells

Authors

  • Maitreyi Subramanian,

    1. Department of Biotechnology, Indian Institute of Technology Madras, Chennai, Tamil Nadu, India
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  • Srinivasa R. Rao,

    1. Department of Biotechnology, Indian Institute of Technology Madras, Chennai, Tamil Nadu, India
    2. Nuffield Department of Surgical Sciences, University of Oxford, Oxfordshire, OX3 7LD, United Kingdom
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  • Pooja Thacker,

    1. Department of Biotechnology, Indian Institute of Technology Madras, Chennai, Tamil Nadu, India
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  • Suvro Chatterjee,

    1. AU-KBC Research Centre, Anna University, Chennai, Tamil Nadu, India
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  • Devarajan Karunagaran

    Corresponding author
    1. Department of Biotechnology, Indian Institute of Technology Madras, Chennai, Tamil Nadu, India
    • Correspondence to: Prof. Devarajan Karunagaran, Department of Biotechnology, Indian Institute of Technology Madras, Chennai, Tamil Nadu, 600036, India. E-mail: karuna@iitm.ac.in

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  • The concept of this study was from MS and DK. All authors contributed to the study design. MS was primarily responsible for experimentation and data analysis. SRR contributed to cloning and luciferase reporter assays and PT contributed to the immunoblotting assays. DK and SC contributed to the research implementation of the study. MS was primarily responsible for paper preparation. DK and SRR helped draft and critically revise the paper. All authors reviewed and approved the final version of the paper.
  • Disclosures: The authors declare that they have no conflicting or competing interests, financial or otherwise.

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.

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