Gene Set: IKEDA_MIR133_TARGETS_UP

Standard name IKEDA_MIR133_TARGETS_UP
Systematic name M2377
Brief description Genes up-regulated in hypertrophic hearts (due to expression of constitutively active form of PPP3CA [GeneID=5530]) and predicted to be targets of miR-133 microRNA.
Full description or abstract Calcium signaling is a central regulator of cardiomyocyte growth and function. Calmodulin is a critical mediator of calcium signals. Because the amount of calmodulin within cardiomyocytes is limiting, the precise control of calmodulin expression is important for the regulation of calcium signaling. In this study, we show for the first time that calmodulin levels are regulated posttranscriptionally in heart failure. The cardiomyocyte-restricted microRNA miR-1 inhibited the translation of calmodulin-encoding mRNAs via highly conserved target sites within their 3' untranslated regions. In keeping with its effect on calmodulin expression, miR-1 downregulated calcium-calmodulin signaling through calcineurin to NFAT. miR-1 also negatively regulated the expression of Mef2a and Gata4, key transcription factors that mediate calcium-dependent changes in gene expression. Consistent with the downregulation of these hypertrophy-associated genes, miR-1 attenuated cardiomyocyte hypertrophy in cultured neonatal rat cardiomyocytes and in the intact adult heart. Our data indicate that miR-1 regulates cardiomyocyte growth responses by negatively regulating the calcium signaling components calmodulin, Mef2a, and Gata4.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 19188439   Authors: Ikeda S,He A,Kong SW,Lu J,Bejar R,Bodyak N,Lee KH,Ma Q,Kang PM,Golub TR,Pu WT
Exact source Table 3S: miR-133 targets: Rel Expr (CN/Ntg) > 1
Related gene sets (show 5 additional gene sets from the source publication)

(show 277 gene sets from the same authors)
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Organism Mus musculus
Contributed by Arthur Liberzon (MSigDB Team)
Source platform Mouse430_2
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Version history 3.1: First introduced

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