Coordinated regulation of cell cycle transcripts by p53-Inducible microRNAs, miR-192 and miR-215

Cancer Res. 2008 Dec 15;68(24):10105-12. doi: 10.1158/0008-5472.CAN-08-1846.


Cell cycle arrest in response to DNA damage is an important antitumorigenic mechanism. MicroRNAs (miRNAs) were recently shown to play key regulatory roles in cell cycle progression. For example, miR-34a is induced in response to p53 activation and mediates G(1) arrest by down-regulating multiple cell cycle-related transcripts. Here we show that genotoxic stress promotes the p53-dependent up-regulation of the homologous miRNAs miR-192 and miR-215. Like miR-34a, activation of miR-192/215 induces cell cycle arrest, suggesting that multiple miRNA families operate in the p53 network. Furthermore, we define a downstream gene expression signature for miR-192/215 expression, which includes a number of transcripts that regulate G(1) and G(2) checkpoints. Of these transcripts, 18 transcripts are direct targets of miR-192/215, and the observed cell cycle arrest likely results from a cooperative effect among the modulations of these genes by the miRNAs. Our results showing a role for miR-192/215 in cell proliferation combined with recent observations that these miRNAs are underexpressed in primary cancers support the idea that miR-192 and miR-215 function as tumor suppressors.

MeSH terms

  • Cell Cycle / genetics*
  • Cell Division / genetics
  • DNA Damage
  • DNA, Neoplasm / biosynthesis
  • DNA, Neoplasm / genetics
  • G1 Phase / genetics
  • G2 Phase / genetics
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Gene Silencing
  • Genes, p53
  • HCT116 Cells
  • Humans
  • MicroRNAs / biosynthesis
  • MicroRNAs / genetics*
  • Neoplasms / genetics*
  • Neoplasms / metabolism
  • Neoplasms / pathology*
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Transfection
  • Tumor Suppressor Protein p53 / biosynthesis
  • Tumor Suppressor Protein p53 / genetics*
  • Up-Regulation


  • DNA, Neoplasm
  • MicroRNAs
  • RNA, Messenger
  • TP53 protein, human
  • Tumor Suppressor Protein p53