Reciprocal regulation of microrna-1 and insulin-like growth factor-1 signal transduction cascade in cardiac and skeletal muscle in physiological and pathological conditions

L Elia, R Contu, M Quintavalle, F Varrone, C Chimenti, Ma Russo, V Cimino, Laura De Marinis Grasso, Andrea Frustaci, D Catalucci, G. Condorelli

Risultato della ricerca: Contributo in rivistaArticolo in rivista

289 Citazioni (Scopus)


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. © 2009 American Heart Association, Inc.
Lingua originaleEnglish
pagine (da-a)2377-2385
Numero di pagine9
Stato di pubblicazionePubblicato - 2009


  • Animals
  • Base Sequence
  • Cell Line
  • Cells, Cultured
  • Female
  • Humans
  • Insulin-Like Growth Factor I
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • MicroRNAs
  • Middle Aged
  • Molecular Sequence Data
  • Muscle, Skeletal
  • Myocytes, Cardiac
  • Signal Transduction
  • acromegaly
  • animal experiment
  • animal model
  • animal tissue
  • article
  • bioinformatics
  • cell differentiation
  • cell growth
  • chemical analysis
  • controlled study
  • correlation analysis
  • gene expression regulation
  • gene overexpression
  • gene targeting
  • growth hormone
  • heart arrhythmia
  • heart development
  • heart failure
  • heart muscle
  • heart muscle biopsy
  • heart ventricle hypertrophy
  • male
  • messenger RNA
  • microRNA
  • mouse
  • nonhuman
  • priority journal
  • regulatory mechanism
  • signal transduction
  • skeletal muscle
  • somatomedin C
  • somatomedin C receptor
  • transcription factor FKHRL1, 3' untranslated region
  • transcription regulation, Adult


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