Systematic name M18120
Brief description Genes down-regulated in HCT116 cells (colon cancer) by expression of MIR192 or MIR215 [GeneID=406967;406997] at 24 h.
Full description or abstract 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.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 19074876   Authors: Georges SA,Biery MC,Kim SY,Schelter JM,Guo J,Chang AN,Jackson AL,Carleton MO,Linsley PS,Cleary MA,Chau BN
Exact source Table ES
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Organism Homo sapiens
Contributed by Jessica Robertson (MSigDB Team)
Source platform HUMAN_GENE_SYMBOL
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Version history 3.0: First introduced

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