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| A microRNA component of the p53 tumour suppressor network |
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| Author(s): He L (He, Lin), He XY (He, Xingyue), Lim LP (Lim, Lee P.), De Stanchina E (De Stanchina, Elisa), Xuan ZY (Xuan, Zhenyu), Liang Y (Liang, Yu), Xue W (Xue, Wen), Zender L (Zender, Lars), Magnus J (Magnus, Jill), Ridzon D (Ridzon, Dana), Jackson AL (Jackson, Aimee L.), Linsley PS (Linsley, Peter S.), Chen CF (Chen, Caifu), Lowe SW (Lowe, Scott W.), Cleary MA (Cleary, Michele A.), Hannon GJ (Hannon, Gregory J.) |
| Source: NATURE Volume: 447 Issue: 7148 Pages: 1130-U16 Published: JUN 28 2007 |
| Times Cited: 237 References: 29 |
| Abstract: A global decrease in microRNA (miRNA) levels is often observed in human cancers(1,2), indicating that small RNAs may have an intrinsic function in tumour suppression. To identify miRNA components of tumour suppressor pathways, we compared miRNA expression profiles of wild-type and p53-deficient cells. Here we describe a family of miRNAs, miR-34a-c, whose expression reflected p53 status. Genes encoding miRNAs in the miR-34 family are direct transcriptional targets of p53, whose induction by DNA damage and oncogenic stress depends on p53 both in vitro and in vivo. Ectopic expression of miR-34 induces cell cycle arrest in both primary and tumour-derived cell lines, which is consistent with the observed ability of miR-34 to downregulate a programme of genes promoting cell cycle progression. The p53 network suppresses tumour formation through the coordinated activation of multiple transcriptional targets, and miR-34 may act in concert with other effectors to inhibit inappropriate cell proliferation. |
| Document Type: Article |
| Language: English |
| Reprint Address: Cleary, MA (reprint author), Rosetta Inpharmat, 401 Terry Ave N, Seattle, WA 98109 USA |
Addresses:
1. Rosetta Inpharmat, Seattle, WA 98109 USA
2. Cold Spring Harbor Lab, Howard Hughes Med Inst, Watson Sch Biol Sci, Cold Spring Harbor, NY 11724 USA
3. SUNY Stony Brook, Genet Program, Stony Brook, NY 11794 USA
4. Appl Biosyst Inc, Adv Res & Technol, Foster City, CA 94404 USA |
| Publisher: NATURE PUBLISHING GROUP, MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND |
| Subject Category: Multidisciplinary Sciences |
| IDS Number: 183HT |
| ISSN: 0028-0836 |
| DOI: 10.1038/nature05939 |
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