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Overexpression of microRNA ‐23a‐5p induces myocardial infarction by promoting cardiomyocyte apoptosis through inhibited of PI3K / AKT signalling pathway
Author(s) -
Huang Jiechun,
Jiang Rongrong,
Chu Xianglin,
Wang Fangrui,
Sun Xiaotian,
Wang Yiqing,
Pang Liewen
Publication year - 2020
Publication title -
cell biochemistry and function
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.933
H-Index - 61
eISSN - 1099-0844
pISSN - 0263-6484
DOI - 10.1002/cbf.3536
Subject(s) - pi3k/akt/mtor pathway , protein kinase b , apoptosis , microrna , microbiology and biotechnology , phosphorylation , biology , signal transduction , cancer research , myocardial infarction , chemistry , medicine , gene , biochemistry
Myocardial infarction (MI) leads to cardiac remodelling and heart failure. Cardiomyocyte apoptosis is considered a critical pathological phenomenon accompanying MI, but the pathogenesis mechanism remains to be explored. MicroRNAs (miRs), with the identity of negative regulator of gene expression, exist as an important contributor to apoptosis. During the experiment of this study, MI mice models were successfully established and sequencing data showed that the expression of miR‐23a‐5p was significantly enhanced during MI progression. Further steps were taken and it showed that apoptosis of cardiac cells weakened as miR‐23a‐5p was downregulated and on the contrary that apoptosis strengthened with the overexpression of miR‐23a‐5p. To explore its working mechanisms, bioinformatics analysis was conducted by referring to multi‐databases to predict the targets of miR‐23a‐5p. Further analysis suggested that those downstream genes enriched in several pathways, especially in the PI3K/Akt singling pathway. Furthermore, it demonstrated that miR‐23a‐5p was negatively related to the phosphorylation of PI3K/Akt, which plays a critical role in triggering cell apoptosis during MI. Recilisib‐activated PI3K/Akt singling pathway could restrain apoptosis from inducing miR‐23a‐5p overexpression, and Miltefosine‐blocked PI3K/Akt singling pathway could restrict apoptosis from inhibiting miR‐23a‐5p reduction. In conclusion, these findings revealed the pivotal role of miR‐23a‐5p‐PI3K/Akt axis in regulating apoptosis during MI, introducing this novel axis as a potential indicator to detect ischemic heart disease and it could be used for therapeutic intervention.