Repression of the miR-17-92 cluster by p53 has an important function in hypoxia-induced apoptosis Export

@article{citeulike:5541279, abstract = {We here report that miR-17-92 cluster is a novel target for p53-mediated transcriptional repression under hypoxia. We found the expression levels of miR-17-92 cluster were reduced in hypoxia-treated cells containing wild-type p53, but were unchanged in hypoxia-treated p53-deficient cells. The repression of miR-17-92 cluster under hypoxia is independent of c-Myc. Luciferase reporter assays mapped the region responding to p53-mediated repression to a p53-binding site in the proximal region of the miR-17-92 promoter. Chromatin immunoprecipitation (ChIP), Re-ChIP and gel retardation assays revealed that the binding sites for p53- and the TATA-binding protein (TBP) overlap within the miR-17-92 promoter; these proteins were found to compete for binding. Finally, we show that pri-miR-17-92 expression correlated well with p53 status in colorectal carcinomas. Over-express miR-17-92 cluster markedly inhibits hypoxia-induced apoptosis, whereas blocked miR-17-5p and miR-20a sensitize the cells to hypoxia-induced apoptosis. These data indicated that p53-mediated repression of miR-17-92 expression likely has an important function in hypoxia-induced apoptosis, and thus further our understanding of the tumour suppressive function of p53.}, author = {Yan, Hong-li and Xue, Geng and Mei, Qian and Wang, Yu-zhao and Ding, Fei-xiang and Liu, Mo-Fang and Lu, Ming-Hua and Tang, Ying and Yu, Hong-yu and Sun, Shu-han}, citeulike-article-id = {5541279}, citeulike-linkout-0 = {http://dx.doi.org/10.1038/emboj.2009.214}, citeulike-linkout-1 = {http://dx.doi.org/10.1038/emboj2009214a}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/19696742}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=19696742}, day = {20}, doi = {10.1038/emboj.2009.214}, issn = {1460-2075}, journal = {The EMBO Journal}, keywords = {apoptosis, cellcycle, function, mirna, regulation}, month = {August}, number = {18}, pages = {2719--2732}, posted-at = {2009-10-09 11:20:39}, priority = {2}, publisher = {Nature Publishing Group}, title = {Repression of the miR-17-92 cluster by p53 has an important function in hypoxia-induced apoptosis}, url = {http://dx.doi.org/10.1038/emboj.2009.214}, volume = {28}, year = {2009} }

TY - JOUR ID - citeulike:5541279 L3 - citeulike-article-id:5541279 N2 - We here report that miR-17-92 cluster is a novel target for p53-mediated transcriptional repression under hypoxia. We found the expression levels of miR-17-92 cluster were reduced in hypoxia-treated cells containing wild-type p53, but were unchanged in hypoxia-treated p53-deficient cells. The repression of miR-17-92 cluster under hypoxia is independent of c-Myc. Luciferase reporter assays mapped the region responding to p53-mediated repression to a p53-binding site in the proximal region of the miR-17-92 promoter. Chromatin immunoprecipitation (ChIP), Re-ChIP and gel retardation assays revealed that the binding sites for p53- and the TATA-binding protein (TBP) overlap within the miR-17-92 promoter; these proteins were found to compete for binding. Finally, we show that pri-miR-17-92 expression correlated well with p53 status in colorectal carcinomas. Over-express miR-17-92 cluster markedly inhibits hypoxia-induced apoptosis, whereas blocked miR-17-5p and miR-20a sensitize the cells to hypoxia-induced apoptosis. These data indicated that p53-mediated repression of miR-17-92 expression likely has an important function in hypoxia-induced apoptosis, and thus further our understanding of the tumour suppressive function of p53. IS - 18 JF - The EMBO Journal SN - 1460-2075 EP - 2732 TI - Repression of the miR-17-92 cluster by p53 has an important function in hypoxia-induced apoptosis PB - Nature Publishing Group VL - 28 SP - 2719 KW - apoptosis KW - cellcycle KW - function KW - mirna KW - regulation AU - Yan, Hong-li AU - Xue, Geng AU - Mei, Qian AU - Wang, Yu-zhao AU - Ding, Fei-xiang AU - Liu, Mo-Fang AU - Lu, Ming-Hua AU - Tang, Ying AU - Yu, Hong-yu AU - Sun, Shu-han PY - 2009/08/20/ UR - http://dx.doi.org/10.1038/emboj.2009.214 ER -