Abstract Acute myocardial infarction (AMI) represents a severe coronary heart disease with relatively high rate of mortality and usually can lead to the damage of the myocardial tissues. Reperfusion of the ischemic myocardial tissues can minimize AMI-induced damage. As far as we know, the molecular mechanisms underlying ischemia/reperfusion (I/R)-induced injury remains elusive. This study was undertaken to explore the role of miR-1247-3p in regulating myocardial I/R injury. The hypoxia/reoxygenation (H/R)-treated H9c2 cells showed a decreased cell viability and mitochondrial membrane potential with an increase in the apoptosis; furthermore, miR-1247-3p was down-regulated in these cells. MiR-1247-3p overexpression attenuated H/R-induced H9c2 cell injury; while miR-1247-3p knockdown in H9c2 cells exhibited similar effects being observed in H/R-treated cells. The bioinformatics prediction revealed Bcl-2-like protein 11 (BCL2L11) and caspase-2 were two potential targets for miR-1247-3p, and functional assays confirmed that miR-1247-3p targeted both BCL2L11 and caspase-2 3′ untranslated regions, which lead to the repressed expression of these genes. Silencing of BCL2L11 and caspase-2 both, respectively, counteracted the H9c2 cell injury caused by H/R treatment. Moreover, BCL2L11 and caspase-2 overexpression, respectively, impaired the protective effects of miR-1247-3p overexpression on H/R-treated H9c2 cells. The data in the present investigation revealed that miR-1247-3p restoration exhibited protective effects on H/R-induced cardiomyocyte injury through targeting BCL2L11 and caspase-2, implying that miR-1247-3p along with caspase-2/BCL2L11 signaling may provide novel sight for a better understating of I/R-induced myocardial damage. The role of miR-1247-3p might be further confirmed in animal models and clinical studies.

中文翻译：

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MiR-1247-3p 通过靶向 BCL2L11 和 caspase-2 保护大鼠心肌细胞免受缺氧/复氧诱导的损伤

摘要 急性心肌梗死（AMI）是一种严重的冠心病，死亡率较高，通常会导致心肌组织损伤。缺血心肌组织的再灌注可以最大限度地减少 AMI 引起的损伤。据我们所知，缺血/再灌注 (I/R) 诱导损伤的分子机制仍然难以捉摸。本研究旨在探讨 miR-1247-3p 在调节心肌 I/R 损伤中的作用。缺氧/复氧 (H/R) 处理的 H9c2 细胞显示细胞活力和线粒体膜电位降低，细胞凋亡增加；此外，miR-1247-3p 在这些细胞中被下调。MiR-1247-3p 过表达减弱了 H/R 诱导的 H9c2 细胞损伤；而 H9c2 细胞中的 miR-1247-3p 敲低表现出类似的效果，在 H/R 处理的细胞中观察到。生物信息学预测显示 Bcl-2 样蛋白 11 (BCL2L11) 和 caspase-2 是 miR-1247-3p 的两个潜在靶标，功能测定证实 miR-1247-3p 同时靶向 BCL2L11 和 caspase-2 3' 非翻译区，这导致这些基因的表达受到抑制。BCL2L11 和 caspase-2 的沉默分别抵消了 H/R 治疗引起的 H9c2 细胞损伤。此外，BCL2L11 和 caspase-2 过表达分别削弱了 miR-1247-3p 过表达对 H/R 处理的 H9c2 细胞的保护作用。本研究中的数据表明，miR-1247-3p 修复通过靶向 BCL2L11 和 caspase-2 对 H/R 诱导的心肌细胞损伤具有保护作用，这意味着 miR-1247-3p 以及 caspase-2/BCL2L11 信号可能为更好地低估 I/R 诱导的心肌损伤提供新的视角。miR-1247-3p 的作用可能在动物模型和临床研究中得到进一步证实。