MicroRNA-26a/b-5p promotes myocardial infarction-induced cell death by downregulating cytochrome c oxidase 5a

Abstract

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.

Heart attack: Possible biomarker may lead to cell repair treatments

Monitoring the activity of two microRNAs, small non-coding RNAs, may provide a useful biomarker for heart attack prognosis and inform novel treatments for repairing heart cells. Ki-Chul Hwang and Jung-Won Choi at the Catholic Kwandong University in Gangwon-do, South Korea, and co-workers examined potential causative factors for heart attacks by exploring the activity of microRNAs in rat models and heart cell cultures. They found that levels of a key protein involved in maintaining mitochondrial function and energy metabolism, cytochrome c oxidase subunit 5a (Cox5a), were significantly decreased in heart cells during oxygen deprivation. Further, they identified two microRNAs that acted to inhibit Cox5a after a heart attack. Suppressing these two microRNAs could boost Cox5a activity and limit cell death, although the authors urge caution because microRNAs also play physiological roles in the body.