p16(INK4a) translation suppressed by miR-24

PLoS One. 2008 Mar 26;3(3):e1864. doi: 10.1371/journal.pone.0001864.

Abstract

Background: Expression of the tumor suppressor p16(INK4a) increases during aging and replicative senescence.

Methodology/principal findings: Here, we report that the microRNA miR-24 suppresses p16 expression in human diploid fibroblasts and cervical carcinoma cells. Increased p16 expression with replicative senescence was associated with decreased levels of miR-24, a microRNA that was predicted to associate with the p16 mRNA coding and 3'-untranslated regions. Ectopic miR-24 overexpression reduced p16 protein but not p16 mRNA levels. Conversely, introduction of antisense (AS)-miR-24 blocked miR-24 expression and markedly enhanced p16 protein levels, p16 translation, and the production of EGFP-p16 reporter bearing the miR-24 target recognition sites.

Conclusions/significance: Together, our results suggest that miR-24 represses the initiation and elongation phases of p16 translation.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Base Sequence
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics*
  • DNA Primers
  • HeLa Cells
  • Humans
  • MicroRNAs / physiology*
  • Mutagenesis, Site-Directed
  • Protein Biosynthesis*

Substances

  • Cyclin-Dependent Kinase Inhibitor p16
  • DNA Primers
  • MicroRNAs