| First Author | Elia L | Year | 2009 |
| Journal | Circulation | Volume | 120 |
| Issue | 23 | Pages | 2377-85 |
| PubMed ID | 19933931 | Mgi Jnum | J:168129 |
| Mgi Id | MGI:4881905 | Doi | 10.1161/CIRCULATIONAHA.109.879429 |
| Citation | Elia L, et al. (2009) Reciprocal regulation of microRNA-1 and insulin-like growth factor-1 signal transduction cascade in cardiac and skeletal muscle in physiological and pathological conditions. Circulation 120(23):2377-85 |
| abstractText | 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. |
