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


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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