MiRNA-488-3p suppresses acute myocardial infarction-induced cardiomyocyte apoptosis via targeting ZNF791

H.-F. Zheng, J. Sun, Z.-Y. Zou, Y. Zhang, G.-Y. Hou

ICU, Chongqing General Hospital, Chongqing, China. houguy@qq.com

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• Cardiology

OBJECTIVE: The aim of this study was to elucidate the potential function of microRNA-488-3p (miRNA-488-3p) in the pathogenesis of acute myocardial infarction (AMI).
MATERIALS AND METHODS: AMI mice constructed by ligation of the anterior descending coronary artery (LAD) were administrated with miRNA-488-3p mimics or negative control, respectively. Infarct size and risk region of AMI mice were determined by triphenyltetrazolium chloride (TTC) staining. The serum level of lactate dehydrogenase (LDH) release in mice was detected by enzyme-linked immunosorbent assay (ELISA). Subsequently, primary cardiomyocytes were isolated from AMI mice administrated with miRNA-488-3p mimics or negative control. LDH release in both hypoxia-preconditioning primary cardiomyocytes and MCM cells was detected. Dual-Luciferase reporter gene assay was used to verify the potential target of miRNA-488-3p. Furthermore, the regulatory effects of miRNA-488-3p and its target ZNF791 on AMI-induced cardiomyocyte apoptosis were evaluated.
RESULTS: MiRNA-488-3p was lowly expressed in AMI mice. Meanwhile, miRNA-488-3p expression decreased in hypoxia-preconditioning primary cardiomyocytes or MCM cells in a time-dependent manner. AMI mice overexpressing miRNA-488-3p showed significantly smaller infarct size and risk region, as well as lower LHD release in serum. Overexpression of miRNA-488-3p markedly down-regulated the protein level of caspase3 in MCM cells. ZNF791 was predicted as the direct target of miRNA-488-3p, which was negatively regulated by miRNA-488-3p. Overexpression of ZNF791 reversed the protective role of miRNA-488-3p in AMI-induced cardiomyocyte apoptosis.
CONCLUSIONS: MiRNA-488-3p is down-regulated in AMI mice, which alleviates AMI-induced cardiomyocyte apoptosis via down-regulating ZNF791.

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