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

Oncogene. 2012 Feb 23;31(8):1045-54. doi: 10.1038/onc.2011.293. Epub 2011 Jul 11.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms
  • Cell Line, Tumor
  • Cell Proliferation
  • Down-Regulation
  • Female
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / metabolism*
  • Gene Expression
  • Gene Expression Regulation, Neoplastic*
  • Genes, Reporter
  • Humans
  • Luciferases, Firefly / biosynthesis
  • Luciferases, Firefly / genetics
  • Matrix Attachment Region Binding Proteins / genetics
  • Matrix Attachment Region Binding Proteins / metabolism*
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Promoter Regions, Genetic
  • RNA Interference

Substances

  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • MIRN155 microRNA, human
  • MIRN7 microRNA, human
  • Matrix Attachment Region Binding Proteins
  • MicroRNAs
  • SATB1 protein, human
  • Luciferases, Firefly