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Suppression of miRNA let-7i-5p promotes cardiomyocyte proliferation and repairs heart function post injury by targetting CCND2 and E2F2.
- Source :
-
Clinical Science . 2/1/2019, Vol. 133 Issue 3, p425-441. 17p. - Publication Year :
- 2019
-
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 lossand gain-of-function of let-7i-5p in CMs in vitro and in vivo. We found that the overexpression of let-7i-5p inhibited CMproliferation, 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. [ABSTRACT FROM AUTHOR]
- Subjects :
- *CELL cycle
*INFARCTION
*CELL cycle regulation
*HEART
Subjects
Details
- Language :
- English
- ISSN :
- 01435221
- Volume :
- 133
- Issue :
- 3
- Database :
- Academic Search Index
- Journal :
- Clinical Science
- Publication Type :
- Academic Journal
- Accession number :
- 134671365
- Full Text :
- https://doi.org/10.1042/CS20181002