Open AccessIntact p53-Dependent Responses in miR-34–Deficient Mice
Author(s) -
Carla P. Concepcion,
Yoon Chi Han,
Ping Mu,
Ciro Bonetti,
Evelyn Yao,
Aleco D’Andrea,
Joana A. Vidigal,
William P. Maughan,
Paul Ogrodowski,
Andrea Ventura
Publication year - 2012
Publication title -
plos genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.587
H-Index - 233
eISSN - 1553-7404
pISSN - 1553-7390
DOI - 10.1371/journal.pgen.1002797
Subject(s) - biology , microrna , carcinogenesis , apoptosis , suppressor , cancer research , cell cycle , function (biology) , cell cycle checkpoint , microbiology and biotechnology , downregulation and upregulation , in vitro , loss function , phenotype , cell growth , genetics , gene
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.