miR-139-5p is a regulator of metastatic pathways in breast cancer

  1. Nicole Cloonan1,7,10
  1. 1Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, University of Queensland, St Lucia, QLD, Australia 4072
  2. 2Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA
  3. 3The University of Queensland, UQ Centre for Clinical Research (UQCCR), Herston, QLD, Australia 4029
  4. 4The University of Queensland, School of Medicine, Herston, QLD, Australia 4029
  5. 5Pathology Queensland, The Royal Brisbane and Women's Hospital, Herston, QLD, Australia 4029
  6. 6Life Technologies, Austin, Texas 78744, USA
  7. 7QIMR Berghofer Medical Research Institute, Genomic Biology Laboratory, Herston, Australia 4006
  8. 8Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, G61 1BD, United Kingdom
    • 9 Present address: Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK

    Abstract

    Metastasis is a complex, multistep process involved in the progression of cancer from a localized primary tissue to distant sites, often characteristic of the more aggressive forms of this disease. Despite being studied in great detail in recent years, the mechanisms that govern this process remain poorly understood. In this study, we identify a novel role for miR-139-5p in the inhibition of breast cancer progression. We highlight its clinical relevance by reviewing miR-139-5p expression across a wide variety of breast cancer subtypes using in-house generated and online data sets to show that it is most frequently lost in invasive tumors. A biotin pull-down approach was then used to identify the mRNA targets of miR-139-5p in the breast cancer cell line MCF7. Functional enrichment analysis of the pulled-down targets showed significant enrichment of genes in pathways previously implicated in breast cancer metastasis (P < 0.05). Further bioinformatic analysis revealed a predicted disruption to the TGFβ, Wnt, Rho, and MAPK/PI3K signaling cascades, implying a potential role for miR-139-5p in regulating the ability of cells to invade and migrate. To corroborate this finding, using the MDA-MB-231 breast cancer cell line, we show that overexpression of miR-139-5p results in suppression of these cellular phenotypes. Furthermore, we validate the interaction between miR-139-5p and predicted targets involved in these pathways. Collectively, these results suggest a significant functional role for miR-139-5p in breast cancer cell motility and invasion and its potential to be used as a prognostic marker for the aggressive forms of breast cancer.

    Keywords

    Footnotes

    • 10 Corresponding authors

      E-mail s.grimmond{at}uq.edu.au

      E-mail nicole.cloonan{at}qimr.edu.au

    • Freely available online through the RNA Open Access option.

    • Received August 26, 2013.
    • Accepted September 12, 2013.

    This article, published in RNA, is available under a Creative Commons License (Attribution-NonCommercial 3.0 Unported), as described at http://creativecommons.org/licenses/by-nc/3.0/.

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