• Register
X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X

Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.

No
Yes

Intact p53-dependent responses in miR-34-deficient mice.

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.

Pubmed ID: 22844244

Authors

  • Concepcion CP
  • Han YC
  • Mu P
  • Bonetti C
  • Yao E
  • D'Andrea A
  • Vidigal JA
  • Maughan WP
  • Ogrodowski P
  • Ventura A

Journal

PLoS genetics

Publication Data

July 30, 2012

Associated Grants

None

Mesh Terms

  • Animals
  • Apoptosis
  • Cell Cycle Checkpoints
  • Cell Proliferation
  • Cell Transformation, Neoplastic
  • Cells, Cultured
  • Fibroblasts
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mice
  • Mice, Knockout
  • MicroRNAs
  • Tumor Suppressor Protein p53