A microRNA component of the p53 tumour suppressor network

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. (June 2007) A microRNA component of the p53 tumour suppressor network. Nature, 447 (7148). pp. 1130-4. ISSN 1476-4687 (Electronic)

URL: https://www.ncbi.nlm.nih.gov/pubmed/17554337
DOI: 10.1038/nature05939

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.

Item Type: Paper
Uncontrolled Keywords: Animals Cell Cycle/ genetics Cell Division/genetics Cell Line DNA Damage Gene Expression Regulation Mice MicroRNAs/ genetics/ metabolism Substrate Specificity Transcription, Genetic Tumor Suppressor Protein p53/ metabolism
Subjects: diseases & disorders > cancer
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > cell line
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > cell line
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > cell line

bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > miRNA
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > miRNA

organism description > animal > mammal > rodent > mouse
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types > p53
CSHL Authors:
Communities: CSHL labs > Hannon lab
CSHL labs > Jackson lab
CSHL labs > Lowe lab
Depositing User: CSHL Librarian
Date: 28 June 2007
Date Deposited: 15 Nov 2011 15:22
Last Modified: 02 Dec 2016 15:30
PMCID: PMC4590999
Related URLs:
URI: http://repository.cshl.edu/id/eprint/23030

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