miR-155 inhibition represents a potential valuable regulator in mitigating myocardial hypoxia/reoxygenation injury through targeting BAG5 and MAPK/JNK signaling

Increasing evidence has indicated that miR-155 is closely associated with apoptosis, which may protect the myocardium and diminish the infarct area in myocardial ischemia reperfusion injury (IRI). In addition, studies have revealed that miR-155 serves a leading role in promoting fibroblast inflammation, cardiac dysfunction and other aspects of myocardial injury. The present study aimed to uncover the function and potential biological mechanism of miR-155 in myocardial IRI. The rat H9c2 myocardial cells was treated with hypoxia/reoxygenation (H/R) to simulate IRI in vitro. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression levels of miR-155 mRNA. Cell Counting Kit-8 and flow cytometry assays and western blot analysis were applied to determine the biological behaviors of the H/R-treated cells. The association between miR-155 and BAG family molecular chaperone regulator 5 (BAG5) was predicted by bioinformatics software and was confirmed by dual luciferase assay. RT-qPCR and western blot analysis were used to analyze the expression of BAG5. The key proteins involved in mitogen-activated protein kinase (MAPK)/JNK signaling pathway were detected by western blot analysis. The data from the RT-qPCR assay indicated that the expression of miR-155 was markedly upregulated in the H/R model, and that downregulation of miR-155 may promote cell proliferation and inhibit cell apoptosis, and vice versa. BAG5, which was downregulated in the H/R model, was confirmed as a target of miR-155 and negatively modulated by miR-155. The key proteins involved in MAPK/JNK signaling, which were highly expressed in the H/R model, were suppressed by treatment with the miR-155 inhibitor, and overexpression of BAG5 promoted the protective effect of miR-155 inhibition on cell injury caused by H/R. In addition, the expression patterns of hypoxia-inducible factor 1-α and von Hippel-Lindau were altered following different treatments. Taken together, the data from the present study indicated that miR-155 inhibition represented a potential treatment strategy to improve myocardial H/R injury, which may be associated with targeting BAG5 and inhibition of the MAPK/JNK pathway.