hsa-miR-1

cardiac hypertrophy

Relationship type:

Causal

Detection method for miRNA expression:

northern blot, qRT-PCR etc

down-regulated

Validated targets of miRNA from the reference:

calmodulin, Mef2a, Gata4

Validated targets of miRNA from TarBase:

GJA1,Hand2,HDAC4,TMSB4X : More...

Description:

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, precise control of calmodulin expression is important for regulation of calcium signaling. In this study, we show for the first time that calmodulin levels are regulated post-transcriptionally in heart failure. The cardiomyocyte-restricted microRNA miR-1 inhibited 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 expression of Mef2a and Gata4, key transcription factors that mediate calcium-dependent changes in gene expression. Consistent with 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.

Reference:

microRNA-1 negatively regulates expression of the hypertrophy-associated genes calmodulin and Mef2a. | PMID:19188439
Ikeda S, He A, Kong SW, Lu J, Bejar R, Bodyak N, Lee KH, Ma Q, Kang PM, Golub TR, Pu WT.
Mol Cell Biol. 2009 Feb 2. [Epub ahead of print]