Abstract
Myocardial infarction (MI) is a great threat to patients all over the word. MicroRNAs (miRNAs) are a group of non-coding RNAs and can regulate initiation and progression of MI. The current research aimed to investigate the role of miR-467a-5p in MI. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was conducted to detective relative expression of miR-467a-5p in cardiac tissues and mouse cardiomyocytes (MCMs). Hematoxylin and eosin staining was used to reveal the histology of the myocardium. Echocardiography was utilized to reveal cardiac function of mice. Flow cytometer analysis was used to reveal cell apoptosis. Luciferase reporter assay was applied for determining the binding capacity between molecules. We discovered that the level of miR-467a-5p was up-regulated in MI mice and in MCMs induced by H2O2 or hypoxia. Functionally, an elevation of left ventricular end-diastolic diameter and left ventricular end-systolic diameter, as well as a decrease of left ventricular ejection fraction and left ventricular fractional shortening were observed in MI mice. In addition, deficiency of miR-467a-5p improved MI in mice by increasing the contents of lactate dehydrogenase, creatine kinase and malondialdehyde and reducing the activity of superoxide dismutase in serum. Moreover, silencing of miR-467a-5p reversed hypoxia-induced apoptosis of MCMs. Mechanistically, zinc finger E-box binding homeobox 1 (ZEB1) was confirmed as the target of miR-467a-5p. Moreover, miR-467a-5p negatively regulated ZEB1 level in MI mice and MCMs. Finally, the promotive effect of miR-467a-5p inhibition on cell apoptosis was reversed by knockdown of ZEB1. All the experimental results demonstrate that miR-467a-5p aggravates MI by modulating ZEB1 expression in mice, which may provide a novel therapeutic strategy for MI.
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The datasets used during the current study are available from the corresponding author on reasonable request.
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Huang, W., Cao, Y., Chen, C. et al. MiR-467a-5p aggravates myocardial infarction by modulating ZEB1 expression in mice. J Mol Histol 52, 767–780 (2021). https://doi.org/10.1007/s10735-021-09978-w
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DOI: https://doi.org/10.1007/s10735-021-09978-w