Silencing Long Noncoding RNA CRNDE Alleviates Hypoxia-Induced Myocardial Cell Injury by Inhibiting the NLRP3/ASC Pathway.

Myocardial ischemia-induced cell injury involves the concurrent occurrence of pyroptosis, apoptosis, and oxidative stress, whereas its upstream regulatory mechanism remains unclear. The present study aimed to investigate the functional association between long noncoding RNA CRNDE and the NLRP3/ASC pathway in H9c2 cardiomyocytes subjected to hypoxia-induced injury. Using H9c2 cardiomyocytes as the research model, a hypoxia-induced injury model was constructed, shRNA-mediated knockdown of CRNDE was performed, and functional rescue experiments were conducted in combination with an NLRP3 agonist. Results showed that hypoxia treatment significantly upregulated the expression level of CRNDE in H9c2 cells, and this upregulation was significantly positively correlated with the activation of the NLRP3/ASC pathway. Knockdown of CRNDE specifically inhibited the mRNA and protein expression of key molecules in the NLRP3/ASC pathway (NLRP3, ASC, Caspase-1, GSDMD); reduced the secretion of inflammatory factors IL-1β and IL-18; decreased the cell apoptosis rate; and improved oxidative stress imbalance. RNA FISH assay confirmed that CRNDE was localized in the cytoplasm of H9c2 cells; knockdown of CRNDE alleviated hypoxia-induced mitochondrial damage, G1/S phase cell cycle arrest, and impairment of cell membrane integrity, and the above protective effects could be reversed by the NLRP3 agonist. In conclusion, CRNDE is closely associated with hypoxia-induced cardiomyocyte injury, and its effects in mediating pyroptosis, apoptosis, and oxidative stress rely on activation of the NLRP3/ASC pathway. Targeting CRNDE may provide a supplementary strategy for the treatment of myocardial ischemia-related diseases.