Silencing of MiR-329-3p Protects against Myocardial Ischemia-Reperfusion Injury by Regulating the Wnt/β-catenin Pathway via Nemo-Like Kinase

Acute myocardial infarction is a major global cause of death. Myocardial ischemia-reperfusion (MI/R) injury occurs immediately after coronary reperfusion and exacerbates myocardial ischemia.Our work aims to elucidate the role and targets of miR-329-3p, as well as the signaling pathways involved in MI/R injury.AC16 cells were subjected to hypoxia/reoxygenation (H/R) to construct an MI/R injury model. miR-329-3p and Nemo-like kinase (NLK) expression were detected by RT-qPCR. Cell viability and apoptosis were assessed using CCK-8 and flow cytometry. ELISA and commercially available kits were used to examine the concentrations of inflammatory factors and levels of the myocardial injury markers CK-MB and LDH. Western blot analysis was used to assess key protein expression in the WNT/β-catenin pathway. Dual luciferase reporter and RIP assays validated miR-329-3p binding to NLK.miR-329-3p was markedly elevated in H/R-exposed cardiomyocytes, whereas NLK was reduced. Furthermore, the downregulation of miR-329-3p exerted cardioprotection by attenuating H/R-induced apoptosis and inflammatory factor overproduction, as well as CK-MB and LDH leakage. NLK is a target of miR-329-3p. Inhibition of NLK typically impaired the cardioprotection associated with miR-329-3p downregulation and promoted activation of the WNT/β-catenin pathway.Silencing miR-329-3p alleviates MI/R injury by enhancing NLK-mediated inhibition of the WNT/β-catenin pathway, thereby reducing H/R-induced cardiomyocyte apoptosis, oxidative stress, and inflammation.