Intact p53-dependent responses in miR-34-deficient mice Journal Article


Authors: Concepcion, C. P.; Han, Y. C.; Mu, P.; Bonetti, C.; Yao, E.; D'Andrea, A.; Vidigal, J. A.; Maughan, W. P.; Ogrodowski, P.; Ventura, A.
Article Title: Intact p53-dependent responses in miR-34-deficient mice
Abstract: MicroRNAs belonging to the miR-34 family have been proposed as critical modulators of the p53 pathway and potential tumor suppressors in human cancers. To formally test these hypotheses, we have generated mice carrying targeted deletion of all three members of this microRNA family. We show that complete inactivation of miR-34 function is compatible with normal development in mice. Surprisingly, p53 function appears to be intact in miR-34-deficient cells and tissues. Although loss of miR-34 expression leads to a slight increase in cellular proliferation in vitro, it does not impair p53-induced cell cycle arrest or apoptosis. Furthermore, in contrast to p53-deficient mice, miR-34-deficient animals do not display increased susceptibility to spontaneous, irradiation-induced, or c-Myc-initiated tumorigenesis. We also show that expression of members of the miR-34 family is particularly high in the testes, lungs, and brains of mice and that it is largely p53-independent in these tissues. These findings indicate that miR-34 plays a redundant function in the p53 pathway and suggest additional p53-independent functions for this family of miRNAs. © 2012 Concepcion et al.
Keywords: controlled study; unclassified drug; nonhuman; protein function; cell proliferation; animal cell; mouse; animals; mice; mice, knockout; animal tissue; dna damage; cells, cultured; apoptosis; microrna; gene expression; embryo; animal experiment; animal model; gene function; in vitro study; protein p53; carcinogenesis; cell transformation, neoplastic; cancer inhibition; gene activation; gene expression regulation, neoplastic; brain; lung; fibroblasts; tumor suppressor protein p53; cell cycle arrest; gene loss; gene inactivation; upregulation; senescence; micrornas; oncogene c myc; cellular stress response; testis; in vivo culture; replicative senescence; microrna 34; cell cycle checkpoints
Journal Title: PLoS Genetics
Volume: 8
Issue: 7
ISSN: 1553-7390
Publisher: Public Library of Science  
Date Published: 2012-07-01
Start Page: e1002797
Language: English
DOI: 10.1371/journal.pgen.1002797
PROVIDER: scopus
PMCID: PMC3406012
PUBMED: 22844244
DOI/URL:
Notes: --- - "Cited By (since 1996): 1" - "Export Date: 4 September 2012" - "Source: Scopus"
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