Myocardial infarction (MI) damage induces various types of cell death, and persistent ischemia causes cardiac contractile decline. An effective therapeutic strategy is needed to reduce myocardial cell death and induce cardiac recovery. Therefore, studies on molecular and genetic biomarkers of MI, such as microRNAs (miRs), have recently been increasing and attracting attention due to the ideal characteristics of miRs. The aim of the present study was to discover novel causative factors of MI using multiomics-based functional experiments. Through proteomic, MALDI-TOF-MS, RNA sequencing, and network analyses of myocardial infarcted rat hearts and in vitro functional analyses of myocardial cells, we found that cytochrome c oxidase subunit 5a (Cox5a) expression is noticeably decreased in myocardial infarcted rat hearts and myocardial cells under hypoxic conditions, regulates other identified proteins and is closely related to hypoxia-induced cell death. Moreover, using in silico and in vitro analyses, we found that miR-26a-5p and miR-26b-5p (miR-26a/b-5p) may directly modulate Cox5a, which regulates hypoxia-related cell death. The results of this study elucidate the direct molecular mechanisms linking miR-26a/b-5p and Cox5a in cell death induced by oxygen tension, which may contribute to the identification of new therapeutic targets to modulate cardiac function under physiological and pathological conditions.

心肌梗塞 (MI) 损伤诱导各种类型的细胞死亡，持续性缺血导致心脏收缩能力下降。需要一种有效的治疗策略来减少心肌细胞死亡并诱导心脏恢复。因此，由于 miRs 的理想特性，最近对 MI 的分子和遗传生物标志物如 microRNAs (miRs) 的研究越来越多并引起了人们的关注。本研究的目的是使用基于多组学的功能实验发现新的 MI 致病因素。通过对心肌梗死大鼠心脏的蛋白质组学、MALDI-TOF-MS、RNA测序和网络分析以及心肌细胞的体外功能分析，我们发现，在缺氧条件下，心肌梗死大鼠心脏和心肌细胞中细胞色素 c 氧化酶亚基 5a (Cox5a) 的表达明显降低，调节其他已识别的蛋白质，并且与缺氧诱导的细胞死亡密切相关。此外，通过计算机和体外分析，我们发现 miR-26a-5p 和 miR-26b-5p (miR-26a/b-5p) 可以直接调节 Cox5a，从而调节缺氧相关的细胞死亡。本研究的结果阐明了 miR-26a/b-5p 和 Cox5a 在氧张力诱导的细胞死亡中的直接分子机制，这可能有助于确定在生理和病理条件下调节心脏功能的新治疗靶点。使用计算机和体外分析，我们发现 miR-26a-5p 和 miR-26b-5p (miR-26a/b-5p) 可以直接调节 Cox5a，从而调节缺氧相关的细胞死亡。本研究的结果阐明了 miR-26a/b-5p 和 Cox5a 在氧张力诱导的细胞死亡中的直接分子机制，这可能有助于确定在生理和病理条件下调节心脏功能的新治疗靶点。使用计算机和体外分析，我们发现 miR-26a-5p 和 miR-26b-5p (miR-26a/b-5p) 可以直接调节 Cox5a，从而调节缺氧相关的细胞死亡。本研究的结果阐明了 miR-26a/b-5p 和 Cox5a 在氧张力诱导的细胞死亡中的直接分子机制，这可能有助于确定在生理和病理条件下调节心脏功能的新治疗靶点。