title: MicroRNA-133 controls cardiac hypertrophy.
abstract: Growing evidence indicates that microRNAs (miRNAs or miRs) are involved in basic cell functions and oncogenesis. Here we report that miR-133 has a critical role in determining cardiomyocyte hypertrophy. We observed decreased expression of both miR-133 and miR-1, which belong to the same transcriptional unit, in mouse and human models of cardiac hypertrophy. In vitro overexpression of miR-133 or miR-1 inhibited cardiac hypertrophy. In contrast, suppression of miR-133 by 'decoy' sequences induced hypertrophy, which was more pronounced than that after stimulation with conventional inducers of hypertrophy. In vivo inhibition of miR-133 by a single infusion of an antagomir caused marked and sustained cardiac hypertrophy. We identified specific targets of miR-133: RhoA, a GDP-GTP exchange protein regulating cardiac hypertrophy; Cdc42, a signal transduction kinase implicated in hypertrophy; and Nelf-A/WHSC2, a nuclear factor involved in cardiogenesis. Our data show that miR-133, and possibly miR-1, are key regulators of cardiac hypertrophy, suggesting their therapeutic application in heart disease.
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore Sanità, 00161 Rome, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Carè
authors.forename: Daniele
authors.initials: D
authors.lastname: Catalucci
authors.forename: Federica
authors.initials: F
authors.lastname: Felicetti
authors.forename: Désirée
authors.initials: D
authors.lastname: Bonci
authors.forename: Antonio
authors.initials: A
authors.lastname: Addario
authors.forename: Paolo
authors.initials: P
authors.lastname: Gallo
authors.forename: Marie-Louise
authors.initials: ML
authors.lastname: Bang
authors.forename: Patrizia
authors.initials: P
authors.lastname: Segnalini
authors.forename: Yusu
authors.initials: Y
authors.lastname: Gu
authors.forename: Nancy D
authors.initials: ND
authors.lastname: Dalton
authors.forename: Leonardo
authors.initials: L
authors.lastname: Elia
authors.forename: Michael V G
authors.initials: MV
authors.lastname: Latronico
authors.forename: Morten
authors.initials: M
authors.lastname: Høydal
authors.forename: Camillo
authors.initials: C
authors.lastname: Autore
authors.forename: Matteo A
authors.initials: MA
authors.lastname: Russo
authors.forename: Gerald W
authors.initials: GW
authors.lastname: Dorn
authors.forename: Oyvind
authors.initials: O
authors.lastname: Ellingsen
authors.forename: Pilar
authors.initials: P
authors.lastname: Ruiz-Lozano
authors.forename: Kirk L
authors.initials: KL
authors.lastname: Peterson
authors.forename: Carlo M
authors.initials: CM
authors.lastname: Croce
authors.forename: Cesare
authors.initials: C
authors.lastname: Peschle
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Condorelli
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000473:pathology; D006332:Cardiomegaly / Q000235:genetics*; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics*; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D051058:Oncogene Protein v-akt / Q000235:genetics; D051381:Rats
chemical_list: D035683:MicroRNAs; D051058:Oncogene Protein v-akt