Intact P53-dependent Responses in MiR-34-deficient Mice

Overview

Journal PLoS Genet

Specialty Genetics

Date 2012 Jul 31

PMID 22844244

Citations 121

Authors

Carla P Concepcion

Yoon-Chi Han

Ping Mu

Ciro Bonetti

Evelyn Yao

Aleco DAndrea

Joana A Vidigal

William P Maughan

Paul Ogrodowski

Andrea Ventura

Affiliations

Soon will be listed here.

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.

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