Suppression of MicroRNA Let-7i-5p Promotes Cardiomyocyte Proliferation and Repairs Heart Function Post Injury by Targeting CCND2 and E2F2.

This study was undertaken to characterize the role of let-7i-5p in the processes of cardiomyocyte cell cycle and proliferation and to reveal the mechanisms thereof. In this study, we used real-time qPCR to determine the upregulated let-7i-5p in cardiomyocytes 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 cardiomyocytes in vitro and in vivo . We found that the overexpression of let-7i-5p inhibited cardiomyocyte proliferation, whereas the suppression of let-7i-5p significantly facilitated cardiomyocyte proliferation. E2F2 and CCND2 were identified as the targets of let-7i-5p, mediating its effect in regulating the cell cycle of cardiomyocytes. 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 cardiomyocyte cell cycle and further impacts proliferation, which may offer a new potential therapeutic strategy for cardiac repair after ischemic injury.

Source: Clinical Science - January 24, 2019 Category: Biomedical Science Authors: Hu, Y., Jin, G., Li, B., Chen, Y., Zhong, L. L., Chen, G., Chen, X., Zhong, J., Liao, W., Liao, Y., Wang, Y., Bin, J. Tags: PublishAheadOfPrint Source Type: research