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.
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 acromegalicpatients, 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.
Authors: C Rommel; S C Bodine; B A Clarke; R Rossman; L Nunez; T N Stitt; G D Yancopoulos; D J Glass Journal: Nat Cell Biol Date: 2001-11 Impact factor: 28.824
Authors: Gianluigi Condorelli; Alessandra Drusco; Giorgio Stassi; Alfonso Bellacosa; Roberta Roncarati; Guido Iaccarino; Matteo A Russo; Yusu Gu; Nancy Dalton; Clarence Chung; Michael V G Latronico; Claudio Napoli; Junichi Sadoshima; Carlo M Croce; John Ross Journal: Proc Natl Acad Sci U S A Date: 2002-09-17 Impact factor: 11.205
Authors: Michael V G Latronico; Stefan Costinean; Maria Luisa Lavitrano; Cesare Peschle; Gianluigi Condorelli Journal: Ann N Y Acad Sci Date: 2004-05 Impact factor: 5.691
Authors: P Briata; W-J Lin; M Giovarelli; M Pasero; C-F Chou; M Trabucchi; M G Rosenfeld; C-Y Chen; R Gherzi Journal: Cell Death Differ Date: 2011-09-02 Impact factor: 15.828