FOXP3 and FOXP3-regulated microRNAs suppress SATB1 in breast cancer cells
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(Accepted version)
Date
2012
Authors
McInnes, N.
Sadlon, T.
Brown, C.
Pederson, S.
Beyer, M.
Schultze, J.
McColl, S.
Goodall, G.
Barry, S.
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Journal article
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Oncogene, 2012; 31(8):1045-1054
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N McInnes, TJ Sadlon, CY Brown, S Pederson, M Beyer, JL Schultze, S McColl, GJ Goodall and SC Barry
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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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© 2012 Macmillan Publishers Limited