MicroRNA-26a/b-5p promotes myocardial infarction-induced cell death by downregulating cytochrome c oxidase 5a.
Animals
Biomarkers
Cell Death
/ genetics
Cell Line
Cell Survival
Computational Biology
/ methods
Disease Susceptibility
Electron Transport Complex IV
/ genetics
Gene Expression Profiling
Gene Expression Regulation
Gene Regulatory Networks
Male
MicroRNAs
/ genetics
Mitochondria
/ genetics
Myocardial Infarction
/ diagnosis
Myocytes, Cardiac
/ metabolism
Proteomics
/ methods
Rats
Journal
Experimental & molecular medicine
ISSN: 2092-6413
Titre abrégé: Exp Mol Med
Pays: United States
ID NLM: 9607880
Informations de publication
Date de publication:
09 2021
09 2021
Historique:
received:
19
02
2021
accepted:
08
07
2021
revised:
06
07
2021
pubmed:
15
9
2021
medline:
30
3
2022
entrez:
14
9
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 34518647
doi: 10.1038/s12276-021-00665-0
pii: 10.1038/s12276-021-00665-0
pmc: PMC8492744
doi:
Substances chimiques
Biomarkers
0
MIRN26 microRNA, rat
0
MicroRNAs
0
Cox5a protein, rat
EC 1.9.3.1
Electron Transport Complex IV
EC 1.9.3.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1332-1343Informations de copyright
© 2021. The Author(s).
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