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FOXP3 and FOXP3-regulated microRNAs suppress SATB1 in breast cancer cells

Oncogene volume 31, pages 1045–1054 (2012)Cite this article

Abstract

The transcription factor FOXP3 has been identified as a tumour suppressor in the breast and prostate epithelia, but little is known about its specific mechanism of action. We have identified a feed-forward regulatory loop in which FOXP3 suppresses the expression of the oncogene SATB1. In particular, we demonstrate that SATB1 is not only a direct target of FOXP3 repression, but that FOXP3 also induces two miRs, miR-7 and miR-155, which specifically target the 3′-UTR of SATB1 to further regulate its expression. We conclude that FOXP3-regulated miRs form part of the mechanism by which FOXP3 prevents the transformation of the healthy breast epithelium to a cancerous phenotype. Approaches aimed at restoring FOXP3 function and the miRs it regulates could help provide new approaches to target breast cancer.

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Acknowledgements

We acknowledge the contributions to this research made by the following co-workers: Danika Hill, Silvia Nobbs, Elizabeth Melville, Suzanne Bresatz, Nicola Eastaff-Leung, Bridget Wilkinson and Marlena Sekutowski. This work was funded by NHMRC Grant 565314 (SCB).

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Author notes

  1. N McInnes and T J Sadlon: These authors contributed equally to this work.

Authors and Affiliations

  1. Women's and Children's Health Research Institute, Molecular Immunology Laboratory, Women's and Children's Hospital, North Adelaide, South Australia, Australia

    N McInnes, T J Sadlon, C Y Brown, S Pederson & S C Barry

  2. Department of Paediatrics, The University of Adelaide, Adelaide, South Australia, Australia

    N McInnes, S Pederson & S C Barry

  3. LIMES-Institute, Laboratory for Genomics and Immunoregulation, University of Bonn, Bonn, Germany

    M Beyer & J L Schultze

  4. Department of Immunology, The University of Adelaide, Adelaide, South Australia, Australia

    S McColl

  5. Centre for Cancer Biology, SA Pathology, Adelaide, South Australia, Australia

    G J Goodall

  6. Department of Medicine, University of Adelaide, Adelaide, South Australia, Australia

    G J Goodall

  7. Department of Gastroenterology, Women's and Children's Hospital, North Adelaide, South Australia, Australia

    S C Barry

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  1. N McInnes
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Correspondence to S C Barry.

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McInnes, N., Sadlon, T., Brown, C. et al. FOXP3 and FOXP3-regulated microRNAs suppress SATB1 in breast cancer cells. Oncogene 31, 1045–1054 (2012). https://doi.org/10.1038/onc.2011.293

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