MicroRNA-133 controls cardiac hypertrophy.
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.
Carè
Alessandra
A
Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore Sanità, 00161 Rome, Italy.
Catalucci
Daniele
D
Felicetti
Federica
F
Bonci
Désirée
D
Addario
Antonio
A
Gallo
Paolo
P
Bang
Marie-Louise
ML
Segnalini
Patrizia
P
Gu
Yusu
Y
Dalton
Nancy D
ND
Elia
Leonardo
L
Latronico
Michael V G
MV
Høydal
Morten
M
Autore
Camillo
C
Russo
Matteo A
MA
Dorn
Gerald W
GW
Ellingsen
Oyvind
O
Ruiz-Lozano
Pilar
P
Peterson
Kirk L
KL
Croce
Carlo M
CM
Peschle
Cesare
C
Condorelli
Gianluigi
G
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
D035683:MicroRNAs; D051058:Oncogene Protein v-akt