MicroRNA 1283 alleviates cardiomyocyte damage caused by hypoxia /reoxygenation via targeting GADD45A and inactivating the JNK and p38 MAPK signaling pathways

Abstract

Background Clarifying the molecular mechanism and identifying markers of myocardial ischemia / reperfusion injury is crucial for the treatment of acute myocardial infarction. aims This study aimed to investigate the roles and underlying regulatory mechanisms of microRNA 1283 (miR-1283) and GADD45A in cardiomyocytes injured by hypoxia / reoxygenation (H / R). methods Bioinformatic analyses were used to determine the expression of GADD45A and miR-1283 based on various datasets from the Gene Expression Omnibus database. Human embryonic cardiomyocytes were subjected to H / R to construct in vitro models. Real -time quantitative polymerase chain reaction and Western blot were used to detect mRNA and protein expression levels, respectively. The binding sites between miR-1283 and GADD45A were predicted by the TargetScan software and verified using dual luciferase reporter assays. Cell viability and apoptosis were detected with the use of Cell Counting Kit 8 and flow cytometry assays. results GADD45A and miR-1283 were upregulated or downregulated in myocardial infarction, respectively. MicroRNA 1283 expression was decreased in cardiomyocytes after H / R treatment. H /R treatment reduced cardiomyocyte viability and enhanced apoptosis, and these effects were abated by transfection of a miR-1283 mimic and strengthened by transfection of a miR-1283 inhibitor. MicroRNA 1283 bound to the 3' untranslated region of GADD45A and decreased the levels of GADD45A, which inhibited proliferation and promoted apoptosis in H / R -induced cardiomyocyte injury. Reintroduction of GADD45A attenuated the effect of miR-1283 on the viability and apoptosis of cardiomyocytes in H / R models. The JNK and p38 MAPK signaling pathways were regulated by the miR-283-GADD45A axis. conclusions The miR-1283-GADD45A axis may protect against H / R -induced cardiomyocyte injury by suppressing the JNK and p38 MAPK pathways.

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“…We identified some miRNAs including hsa-miR-1283, hsa-miR-664b-3p, hsa-miR-579-3p, which targeted multiple regions in the RdRp sequence of BCoV, SARS-CoV, and SARS-CoV-2; these miRNAs have been previously linked with onco-protective roles, indicating their growth regulatory function. For example, hsa-miR-1283 has been connected with cardio-protection and inhibition of apoptosis (Liu et al, 2021), thereby blocking oncogenesis. In addition, this miRNA has also been implicated in hypertension .…”

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