Journal
NATURE
Volume 447, Issue 7148, Pages 1130-U16Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nature05939
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Funding
- NCI NIH HHS [P30 CA008748, K99 CA126186-01, K99 CA126186, P01 CA013106, P01 CA087497] Funding Source: Medline
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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.
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