A microRNA component of the p53 tumour suppressor network

Lin He, Xingyue He, Lee P. Lim, Elisa De Stanchina, Zhenyu Xuan, Yu Liang, Wen Xue, Lars Zender, Jill Magnus, Dana Ridzon, Aimee L. Jackson, Peter S. Linsley, Caifu Chen, Scott W. Lowe, Michele A. Cleary, Gregory J. Hannon

Research output: Contribution to journalArticle

2066 Scopus citations

Abstract

A global decrease in microRNA (miRNA) levels is often observed in human cancers, 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.

Original languageEnglish (US)
Pages (from-to)1130-1134
Number of pages5
JournalNature
Volume447
Issue number7148
DOIs
StatePublished - Jun 28 2007
Externally publishedYes

ASJC Scopus subject areas

  • General

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    He, L., He, X., Lim, L. P., De Stanchina, E., Xuan, Z., Liang, Y., Xue, W., Zender, L., Magnus, J., Ridzon, D., Jackson, A. L., Linsley, P. S., Chen, C., Lowe, S. W., Cleary, M. A., & Hannon, G. J. (2007). A microRNA component of the p53 tumour suppressor network. Nature, 447(7148), 1130-1134. https://doi.org/10.1038/nature05939