BACKGROUND: MicroRNAs (miRNAs/miRs) are small conserved RNA molecules of 22 
nucleotides that negatively modulate gene expression primarily through base 
paring to the 3' untranslated region of target messenger RNAs. The 
muscle-specific miR-1 has been implicated in cardiac hypertrophy, heart 
development, cardiac stem cell differentiation, and arrhythmias through 
targeting of regulatory proteins. In this study, we investigated the molecular 
mechanisms through which miR-1 intervenes in regulation of muscle cell growth 
and differentiation.
METHODS AND RESULTS: On the basis of bioinformatics tools, biochemical assays, 
and in vivo models, we demonstrate that (1) insulin-like growth factor-1 (IGF-1) 
and IGF-1 receptor are targets of miR-1; (2) miR-1 and IGF-1 protein levels are 
correlated inversely in models of cardiac hypertrophy and failure as well as in 
the C2C12 skeletal muscle cell model of differentiation; (3) the activation 
state of the IGF-1 signal transduction cascade reciprocally regulates miR-1 
expression through the Foxo3a transcription factor; and (4) miR-1 expression 
correlates inversely with cardiac mass and thickness in myocardial biopsies of 
acromegalic patients, in which IGF-1 is overproduced after aberrant synthesis of 
growth hormone.
CONCLUSIONS: Our results reveal a critical role of miR-1 in mediating the 
effects of the IGF-1 pathway and demonstrate a feedback loop between miR-1 
expression and the IGF-1 signal transduction cascade.