Melanoma cell invasiveness is regulated by miR-211 suppression of the BRN2 transcription factor

Authors

  • Glen M. Boyle,

    1.  Drug Discovery Group, Division of Cancer & Cell Biology, Queensland Institute of Medical Research, Brisbane, QLD, Australia
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    • These authors contributed equally.

  • Susan L. Woods,

    1.  Oncogenomics Lab, Division of Genetics & Population Health, Queensland Institute of Medical Research, Brisbane, QLD, Australia
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    • These authors contributed equally.

  • Vanessa F. Bonazzi,

    1.  Oncogenomics Lab, Division of Genetics & Population Health, Queensland Institute of Medical Research, Brisbane, QLD, Australia
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  • Mitchell S. Stark,

    1.  Oncogenomics Lab, Division of Genetics & Population Health, Queensland Institute of Medical Research, Brisbane, QLD, Australia
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  • Elke Hacker,

    1.  Oncogenomics Lab, Division of Genetics & Population Health, Queensland Institute of Medical Research, Brisbane, QLD, Australia
    2.  AusSun Research Lab, School of Public Health, Queensland University of Technology, Brisbane, QLD, Australia
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  • Lauren G. Aoude,

    1.  Oncogenomics Lab, Division of Genetics & Population Health, Queensland Institute of Medical Research, Brisbane, QLD, Australia
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  • Ken Dutton-Regester,

    1.  Oncogenomics Lab, Division of Genetics & Population Health, Queensland Institute of Medical Research, Brisbane, QLD, Australia
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  • Anthony L. Cook,

    1.  Melanogenix Group, Division of Molecular Genetics and Development, Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD, Australia
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    • Current address: School of Human Life Sciences, University of Tasmania, Launceston, TAS, Australia.

  • Richard A. Sturm,

    1.  Melanogenix Group, Division of Molecular Genetics and Development, Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD, Australia
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  • Nicholas K. Hayward

    1.  Oncogenomics Lab, Division of Genetics & Population Health, Queensland Institute of Medical Research, Brisbane, QLD, Australia
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Glen M. Boyle, e-mail: Glen.Boyle@qimr.edu.au

Summary

To identify microRNAs potentially involved in melanomagenesis, we compared microRNA expression profiles between melanoma cell lines and cultured melanocytes. The most differentially expressed microRNA between the normal and tumor cell lines was miR-211. We focused on this pigment-cell-enriched miRNA as it is derived from the microphthalmia-associated transcription factor (MITF)-regulated gene, TRPM1 (melastatin). We find that miR-211 expression is greatly decreased in melanoma cells and melanoblasts compared to melanocytes. Bioinformatic analysis identified a large number of potential targets of miR-211, including POU3F2 (BRN2). Inhibition of miR-211 in normal melanocytes resulted in increased BRN2 protein, indicating that endogenous miR-211 represses BRN2 in differentiated cells. Over-expression of miR-211 in melanoma cell lines changed the invasive potential of the cells in vitro through directly targeting BRN2 translation. We propose a model for the apparent non-overlapping expression levels of BRN2 and MITF in melanoma, mediated by miR-211 expression.

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