MicroRNA-30c-1-3p Alleviates Hypoxia-Induced Cardiomyocyte Dysfunction via Tnrc6a Targeting

Background/Objectives: Myocardial infarction (MI) remains a leading cause of death worldwide, primarily resulting from abrupt coronary occlusion that induces severe hypoxia and extensive cardiomyocyte loss. Hypoxia triggers mitochondrial dysfunction, oxidative stress, inflammation, and apoptosis, ultimately compromising cardiac function and promoting adverse cardiac remodeling. MicroRNAs (miRNAs) have emerged as critical regulators of cardiomyocyte survival and stress responses under ischemic conditions; however, the functional roles and molecular mechanisms of many hypoxia-responsive miRNAs remain insufficiently defined. Methods: In this study, we focused on miR-30c-1-3p, which is markedly downregulated during the early phase of MI, and investigated its functional role in hypoxia-induced cardiomyocyte injury. We identified trinucleotide repeat-containing 6A (Tnrc6a), a key component of the miRNA-induced silencing complex, as a potential downstream target. Using primary neonatal rat cardiomyocytes, we performed gain- and loss-of-function experiments, luciferase reporter assays, and Tnrc6a knockdown analyses to evaluate apoptosis, inflammatory cytokine secretion, and release of myocardial injury-related proteins. Results: Restoration of miR-30c-1-3p significantly attenuated hypoxia-induced pro-apoptotic signaling, reduced inflammatory cytokine release, and decreased myocardial injury markers. These protective effects were associated with regulation of the miR-30c-1-3p/Tnrc6a axis. Conclusions: Collectively, our findings identify a previously unappreciated functional role of the miR-30c-1-3p/Tnrc6a axis in hypoxia-induced cardiomyocyte injury and highlight its potential relevance in myocardial stress adaptation.