Overexpression of miR-365a-3p relieves sepsis-induced acute myocardial injury by targeting MyD88/NF-κB pathway.

Background Sepsis often leads to systemic multiple organ dysfunction, with the majority of deaths attributable to acute myocardial injury (AMI). In this study, we aimed to explore the functional role of miR-365a-3p in sepsis induced AMI. Materials and methods The sepsis myocardial injury model was constructed using lipopolysaccharide (LPS) both in vitro and in vivo with selective regulation of miR-365a-3p expression. RT-PCR or western blot was employed to detect the expressions of miR-365a-3p, inflammatory cytokines (TNF-α, IL6, IL-1β), and inflammation-related proteins (NF-κB, I-κB, MyD88) in myocardial tissues and cells. Also, cell counting kit-8 (CCK8) and flow cytometry assays were used measuring cardiomyocyte proliferation and apoptosis, respectively. Furthermore, the targeting relationship between miR-365a-3p and MyD88 was verified with the dual luciferase activity assay. Results MiR-365a-3p was down-regulated in LPS-induced myocardial injury model. MiR-365a-3p overexpression attenuated cardiomyocyte apoptosis, and suppressed the expressions of inflammatory cytokines and proteins. Inhibiting miR-365a-3p, however, produced the opposite effects. Mechanistically, miR-365a-3p targeted the 3'-untranslated region (3'UTR) of MyD88, thereby inactivating MyD88 mediated NF-κB pathway. Conclusion MiR-365a-3p overexpression mitigated sepsis-mediated myocardial injury by inhibiting MyD88-mediated NF-κB activation.