Human Gene Set: IKEDA_MIR1_TARGETS_DN

For the Mouse gene set with the same name, see IKEDA_MIR1_TARGETS_DN

Standard name IKEDA_MIR1_TARGETS_DN
Systematic name M2376
Brief description Genes down-regulated in hypertrophic hearts (due to expression of constitutively active form of PPP3CA [GeneID=5530]) and predicted to be targets of miR-1 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
      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-1 targets: Rel Expr (CN/Ntg) < 1
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Source species Mus musculus
Contributed by Arthur Liberzon (MSigDB Team)
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identifier namespace		 AFFY_Mouse430
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Version history 3.1: First introduced

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