MicroRNA-1 upregulation promotes myocardiocyte proliferation and suppresses apoptosis during heart development

Abstract

Previous studies have investigated the role of microRNAs (miRs) in heart development to reveal the miRNA mechanism of action in congenital heart disease (CHD) in children. The present study aimed to investigate the role of miR‑1 in heart development in P19 cells. The mRNA level for miR‑1 in P19 cells was detected before or after cardiomyocyte differentiation, using reverse transcription‑quantitative polymerase chain reaction analysis. Expression of cardiomyocyte differentiation markers was also analyzed. The effect of miR‑1 overexpression on the viability and apoptosis of differentiated P19 cells was assessed using MTT and Annexin V‑FITC assays, respectively. Furthermore, the effects of miR-1 on expression of markers of cell proliferation and apoptosis were also analyzed in differentiated P19 cells using western blotting. The results demonstrated that P19 cells were successfully differentiated into cardiomyocytes, and that endogenous miR‑1 expression was significantly decreased in differentiated P19 cells compared with undifferentiated P19 cells. Overexpression of miR‑1 resulted in increased viability in differentiated P19 cells and decreased apoptosis, compared with the normal control. In addition, expression of heart and neural crest derivatives expressed transcript 2 (Hand2) was increased in differentiated cells with miR‑1 overexpressed compared with normal cells, while caspase‑3 cleavage was decreased by miR‑1 overexpression. In conclusion, the present study suggested that miR-1 upregulation may be important in regulating cell proliferation and apoptosis in P19 differentiated cardiomyocytes by increasing Hand2 expression and suppressing caspase‑3 cleavage. The present study aimed to provide a theoretical basis for the explanation of the mechanism of CHD and investigate miR‑1 as a potential therapeutic target for its clinical treatment.

Perindopril Improves Cardiac Function by Enhancing the Expression of SIRT3 and PGC-1α in a Rat Model of Isoproterenol-Induced Cardiomyopathy

“…Dysfunction of the respiratory chain further increases ROS production, which creates a positive feedback loop and exacerbates the damage. Moreover, insufficient energy production and myocardial apoptosis are conducive to ventricular remodeling, ultimately leading to the occurrence of HF (Liu et al, 2017). The results of this study suggest that the increased ROS production in myocardial tissues of ISO-induced cardiomyopathy rats is accompanied by the destruction of the mitochondrial ultrastructure, decreased mitochondria numbers, reduced activities of mitochondrial respiratory chain I, II, III, IV, and decreased ATP production; however, PER intervention can ameliorate the disruption of mitochondria, attenuate decreases in mitochondrial numbers, improve respiratory chain function, and increase myocardial ATP content.…”

“…Recent studies (Zhang et al, 2015;Liu et al, 2017) suggest that OS-induced production of excessive ROS induces apoptosis, and myocardial apoptosis causes ventricular remodeling, which ultimately leads to HF (Zhang et al, 2015;Liu et al, 2017).…”

MicroRNA‐1 facilitates hypoxia‐induced injury by targeting NOTCH3

“…miR-1 has been suggested to have an important impact on cardiac pathology. 15 Liu et al 6 suggested that miR-1 overexpression contributed to proliferation but inhibited apoptosis of cardiomyocytes in heart development. However, accruing studies have revealed that miR-1 promoted cardiomyocytes apoptosis and suppressed proliferation under glucose or oxidative stress conditions.…”

“…5 Moreover, previous study suggests that miR-1 contributes to increase of proliferation and inhibition of apoptosis of cardiomyocytes during heart development. 6 However, the function of miR-1 in regulating hypoxia injury as well as its mechanism remains largely unknown.…”

Tongmai Yangxin Pills Improves Cardiac Function by Enhancing the Expression of SIRT3 and PGC-1α in a Rat Model of Isoproterenol-Induced Cardiomyopathy

“…Under the condition of OS, the increase of ROS production in mitochondria may lead to abnormal mitochondrial respiratory chain function, leading to reduced ATP synthesis and activation of endogenous apoptotic pathways. In addition, insu cient energy production and cardiomyocyte apoptosis contribute to ventricular remodeling and ultimately lead to HF (25). The results of this study indicate that the production of ROS in the myocardial tissue of ISO-induced cardiomyopathy rats is accompanied by a decrease in mitochondrial respiratory chain I, II, III, IV activity and ATP production.…”