Dataset Information

FOXP3-miR-146-NF-?B Axis and Therapy for Precancerous Lesions in Prostate.

ABSTRACT: 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-?B 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-?B activation. In addition, prostatic intraepithelial neoplasia lesions were observed in miR-146a-mutant mice as well as in Foxp3-mutant mice. Notably, the NF-?B 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-?B axis has a functional role during tumor initiation in prostate cancer. Targeting the miR-146-NF-?B axis may provide a new therapeutic approach for prostate cancers with FOXP3 defects.

SUBMITTER: Liu R

PROVIDER: S-EPMC4620056 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

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FOXP3-miR-146-NF-κB Axis and Therapy for Precancerous Lesions in Prostate.

Liu Runhua R Yi Bin B Wei Shi S Yang Wei-Hsiung WH Hart Karen M KM Chauhan Priyanka P Zhang Wei W Mao Xicheng X Liu Xiuping X Liu Chang-Gong CG Wang Lizhong L

Cancer research 20150223 8

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 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 reduct ...[more]

PMID: 25712341

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Dataset Information

FOXP3-miR-146-NF-?B Axis and Therapy for Precancerous Lesions in Prostate.

Publications

FOXP3-miR-146-NF-κB Axis and Therapy for Precancerous Lesions in Prostate.

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