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Repression of the miR-17-92 cluster by p53 has an important function in hypoxia-induced apoptosis
文献类型：期刊论文
| 作者 | Yan, HL; Xue, G; Mei, Q; Wang, YZ; Ding, FX; Liu, MF; Lu, MH; Tang, Y; Yu, HY; Sun, SH |
| 刊名 | EMBO JOURNAL
 |
| 出版日期 | 2009 |
| 卷号 | 28期号:18页码:2719-2732 |
| 关键词 | apoptosis hypoxia microRNA 17-92 cluster p53 transcriptional repression |
| 通讯作者 | Sun, SH (reprint author), Second Mil Med Univ, Dept Med Genet, Inst Genet, 800 Xiangyin Rd, Shanghai 200433, Peoples R China.,shsun@vip.sina.com |
| 英文摘要 | 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. The EMBO Journal (2009) 28, 2719-2732. doi: 10.1038/emboj.2009.214; Published online 20 August 2009 |
| 学科主题 | Biochemistry & Molecular Biology; Cell Biology |
| 类目[WOS] | Biochemistry & Molecular Biology ; Cell Biology |
| 关键词[WOS] | TUMOR-SUPPRESSOR GENE ; WILD-TYPE P53 ; TRANSCRIPTIONAL REPRESSION ; MICRORNA CLUSTER ; CANCER-CELLS ; P53-DEPENDENT TRANSACTIVATION ; LUNG CANCERS ; SOLID TUMORS ; C-MYC ; EXPRESSION |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000269842000005 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.143/handle/331003/1280]  |
| 专题 | 上海生化细胞研究所_上海生科院生化细胞研究所 |
| 推荐引用方式 GB/T 7714 | Yan, HL,Xue, G,Mei, Q,et al. Repression of the miR-17-92 cluster by p53 has an important function in hypoxia-induced apoptosis[J]. EMBO JOURNAL,2009,28(18):2719-2732. |
| APA | Yan, HL.,Xue, G.,Mei, Q.,Wang, YZ.,Ding, FX.,...&Sun, SH.(2009).Repression of the miR-17-92 cluster by p53 has an important function in hypoxia-induced apoptosis.EMBO JOURNAL,28(18),2719-2732. |
| MLA | Yan, HL,et al."Repression of the miR-17-92 cluster by p53 has an important function in hypoxia-induced apoptosis".EMBO JOURNAL 28.18(2009):2719-2732. |
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