title: Repression of the miR-17-92 cluster by p53 has an important function in hypoxia-induced apoptosis.
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.
authors.affiliation: Institute of Genetics, Second Military Medical University, Shanghai, China.
authors.forename: Hong-li
authors.initials: HL
authors.lastname: Yan
authors.forename: Geng
authors.initials: G
authors.lastname: Xue
authors.forename: Qian
authors.initials: Q
authors.lastname: Mei
authors.forename: Yu-zhao
authors.initials: YZ
authors.lastname: Wang
authors.forename: Fei-xiang
authors.initials: FX
authors.lastname: Ding
authors.forename: Mo-Fang
authors.initials: MF
authors.lastname: Liu
authors.forename: Ming-Hua
authors.initials: MH
authors.lastname: Lu
authors.forename: Ying
authors.initials: Y
authors.lastname: Tang
authors.forename: Hong-yu
authors.initials: HY
authors.lastname: Yu
authors.forename: Shu-han
authors.initials: SH
authors.lastname: Sun
mesh_terms: D017209:Apoptosis; D001665:Binding Sites; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D006801:Humans; D000860:Hypoxia; D007700:Kinetics; D008156:Luciferases / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics*; D008954:Models, Biological; D005810:Multigene Family; D011401:Promoter Regions, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: C524941:MIRN17 microRNA, human; D035683:MicroRNAs; D016159:Tumor Suppressor Protein p53; D008156:Luciferases
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