MicroRNA-182-5p targets a network of genes involved in DNA repair

  1. Sean M. Grimmond1,6
  1. 1Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD, Australia 4072
  2. 2The University of Queensland, UQ Centre for Clinical Research (UQCCR), Herston, QLD, Australia 4029
  3. 3Diamantina Institute, Princess Alexandra Hospital, The University of Queensland, Woolloongabba, QLD, Australia 4102
  4. 4Life Technologies, Austin, Texas 78744, USA
    • 5 Present address: Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK

    Abstract

    MicroRNAs are noncoding regulators of gene expression, which act by repressing protein translation and/or degrading mRNA. Many have been shown to drive tumorigenesis in cancer, but functional studies to understand their mode of action are typically limited to single-target genes. In this study, we use synthetic biotinylated miRNA to pull down endogenous targets of miR-182-5p. We identified more than 1000 genes as potential targets of miR-182-5p, most of which have a known function in pathways underlying tumor biology. Specifically, functional enrichment analysis identified components of both the DNA damage response pathway and cell cycle to be highly represented in this target cohort. Experimental validation confirmed that miR-182-5p-mediated disruption of the homologous recombination (HR) pathway is a consequence of its ability to target multiple components in that pathway. Although there is a strong enrichment for the cell cycle ontology, we do not see primary proliferative defects as a consequence of miR-182-5p overexpression. We highlight targets that could be responsible for miR-182-5p-mediated disruption of other biological processes attributed in the literature so far. Finally, we show that miR-182-5p is highly expressed in a panel of human breast cancer samples, highlighting its role as a potential oncomir in breast cancer.

    Keywords

    Footnotes

    • 6 Corresponding authors

      E-mail n.cloonan{at}genomicbiology.org

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

    • Received June 13, 2012.
    • Accepted November 14, 2012.

    Freely available online through the RNA Open Access option.

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