Data from FOXP3–miR-146–NF-κB Axis and Therapy for Precancerous Lesions in Prostate

Abstract

<div>Abstract<p>The tumor-suppressive activity of FOXP3 has been observed in tumor initiation, but the underlying mechanism still remains largely unknown. Here, we identified a FOXP3–microRNA-146 (miR-146)–NF-κB axis <i>in vitro</i> and <i>in vivo</i> in prostate cancer cells. We observed that FOXP3 dramatically induced the expression of miR-146a/b, which contributed to transcriptional inhibition of <i>IRAK1</i> and <i>TRAF6</i>, in prostate cancer cell lines. Tissue-specific deletion of <i>Foxp3</i> in mouse prostate caused a significant reduction of miR-146a and upregulation of NF-κB activation. In addition, prostatic intraepithelial neoplasia lesions were observed in miR-146a–mutant mice as well as in <i>Foxp3</i>-mutant mice. Notably, the NF-κB inhibitor bortezomib inhibited cell proliferation and induced apoptosis in prostate epithelial cells, attenuating prostatic intraepithelial neoplasia formation in <i>Foxp3</i>-mutant mice. Our data suggest that the FOXP3–miR-146–NF-κB axis has a functional role during tumor initiation in prostate cancer. Targeting the miR-146–NF-κB axis may provide a new therapeutic approach for prostate cancers with FOXP3 defects. <i>Cancer Res; 75(8); 1714–24. ©2015 AACR</i>.</p></div>