| First Author | Liu R | Year | 2015 |
| Journal | Cancer Res | Volume | 75 |
| Issue | 8 | Pages | 1714-24 |
| PubMed ID | 25712341 | Mgi Jnum | J:220160 |
| Mgi Id | MGI:5632415 | Doi | 10.1158/0008-5472.CAN-14-2109 |
| Citation | Liu R, et al. (2015) FOXP3-miR-146-NF-kappaB Axis and Therapy for Precancerous Lesions in Prostate. Cancer Res 75(8):1714-24 |
| abstractText | 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-kappaB axis in vitro and in vivo in prostate cancer cells. We observed that FOXP3 dramatically induced the expression of miR-146a/b, which contributed to transcriptional inhibition of IRAK1 and TRAF6, in prostate cancer cell lines. Tissue-specific deletion of Foxp3 in mouse prostate caused a significant reduction of miR-146a and upregulation of NF-kappaB activation. In addition, prostatic intraepithelial neoplasia lesions were observed in miR-146a-mutant mice as well as in Foxp3-mutant mice. Notably, the NF-kappaB inhibitor bortezomib inhibited cell proliferation and induced apoptosis in prostate epithelial cells, attenuating prostatic intraepithelial neoplasia formation in Foxp3-mutant mice. Our data suggest that the FOXP3-miR-146-NF-kappaB axis has a functional role during tumor initiation in prostate cancer. Targeting the miR-146-NF-kappaB axis may provide a new therapeutic approach for prostate cancers with FOXP3 defects. |
