FOXP 3 and FOXP 3-regulated microRNAs suppress the expression of SATB 1 in breast cancer cell lines

The transcription factor FOXP3 has been identified as a tumour suppressor in 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 microRNAs; miR-7 and miR-155, which specifically target the 3' UTR of SATB1 to further regulate its expression. We conclude that FOXP3-regulated microRNAs form part of the mechanism by which FOXP3 prevents the transformation of 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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