Exploring miR-3148's impact on Krüppel-like factor 6-driven mitophagy and apoptosis in myocardial ischemic injury.

OBJECTIVE: Myocardial infarction (MI) is a leading cause of death worldwide, accounting for millions of fatalities annually. The injury and repair of cardiomyocytes are closely associated with the changes in gene expression. MicroRNAs could serve as a potential target for MI treatment. This work aims to investigate the role of miR-3148 in mitochondrial dynamics during acute MI (AMI) with a specific focus on its regulatory mechanisms in mitophagy and apoptosis, which could reveal potential therapeutic targets for AMI treatment. MATERIAL AND METHODS: MiR-3148 levels in patients with AMI and experimental models were measured to assess the effects of miR-3148 on cardiomyocyte viability under oxygen and glucose deprivation (OGD). The present investigation involved monitoring mitophagy markers, including PTEN-induced kinase 1 (PINK1), parkin RBR E3 ubiquitin-protein ligase (Parkin), Beclin1, and microtubule-associated protein 1A/1B light chain 3 II/I (LC3 II/I) ratio, as well as apoptotic markers such as cysteine-aspartic acid protease (Caspase) 9, Caspase 3, and cytochrome C (Cyt C). In addition, Krüppel-like factor 6 (KLF6) was examined as a target of miR-3148. RESULTS: MiR-3148 was significantly elevated in patients with AMI and models. MiR-3148 overexpression reduced cardiomyocyte viability, whereas miR-3148 knockdown protected against OGD injury. The inhibition of miR-3148 activated mitophagy, as shown by the increased PINK1, Parkin, Beclin1 levels, and LC3 II/I ratios, and reduced sequestosome 1 (p62), and apoptotic markers levels. MiR-3148 directly targeted KLF6, reducing its expression. The suppression of KLF6 aggravated OGD injury by disrupting PINK1/Parkin-mediated mitophagy and enhancing apoptosis. Attenuating KLF6 expression reversed the protective effects of miR-3148 inhibition, indicating reciprocal regulation. CONCLUSION: In myocardial ischemic injury, miR-3148 modulates PINK1/Parkin-mediated mitophagy and apoptosis through KLF6 regulation. This finding highlights miR-3148 as a key factor in the pathogenesis of AMI and as a potential therapeutic target.