MicroRNA 1283 alleviates cardiomyocyte damage caused by hypoxia /reoxygenation via targeting GADD45A and inactivating the JNK and p38 MAPK signaling pathways
Abstract
Background: Clarifying themolecular 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 miR1283 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.
