Suppression of miRNA let-7i-5p promotes cardiomyocyte proliferation and repairs heart function post injury by targetting CCND2 and E2F2.
Clin Sci (Lond)
; 133(3): 425-441, 2019 02 14.
Article
em En
| MEDLINE
| ID: mdl-30679264
ABSTRACT
MiRNAs regulate the cardiomyocyte (CM) cell cycle at the post-transcriptional level, affect cell proliferation, and intervene in harmed CM repair post-injury. The present study was undertaken to characterize the role of let-7i-5p in the processes of CM cell cycle and proliferation and to reveal the mechanisms thereof. In the present study, we used real-time qPCR (RT-qPCR) to determine the up-regulated let-7i-5p in CMs during the postnatal switch from proliferation to terminal differentiation and further validated the role of let-7i-5p by loss- and gain-of-function of let-7i-5p in CMs in vitro and in vivo We found that the overexpression of let-7i-5p inhibited CM proliferation, whereas the suppression of let-7i-5p significantly facilitated CM proliferation. E2F2 and CCND2 were identified as the targets of let-7i-5p, mediating its effect in regulating the cell cycle of CMs. Supperession of let-7i-5p promoted the recovery of heart function post-myocardial infarction by enhancing E2F2 and CCND2. Collectively, our results revealed that let-7i-5p is involved in the regulation of the CM cell cycle and further impacts proliferation, which may offer a new potential therapeutic strategy for cardiac repair after ischemic injury.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Miócitos Cardíacos
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MicroRNAs
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Proliferação de Células
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Fator de Transcrição E2F2
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Ciclina D2
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Clin Sci (Lond)
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
China