Peng Wang, Yuling Ma, Peirong Zhang, Lijun Xu, Yanwei Cheng, Tai Dou
BACKGROUND AND OBJECTIVES: Acute myocardial infarction (AMI) remains an important driver of cardiovascular mortality. Long non-coding RNA negative regulator of interferon response (NRIR) has been implicated in oxidative stress and apoptotic pathways, but its role in AMI is not yet clear. This study aimed to explore the diagnostic and prognostic significance of NRIR and its potential molecular mechanism in AMI. METHODS: Two hundred twenty-six participants were enrolled, including 102 stable angina pectoris and 124 AMI patients. NRIR expression was quantified, and the diagnostic value was evaluated using receiver operating characteristic. Logistic regression was used to identify risk factors for major adverse cardiovascular events (MACE). H9c2 cardiomyocytes were subjected to oxygen-glucose deprivation (OGD). Cell viability, apoptosis, oxidative stress (ROS, MDA), and mitochondrial function (ATP, NADPH/NADP⁺) were assessed. The interactions between NRIR, miR-515-5p, and SLC40A1 were verified by dual-luciferase assays and functional rescue experiments. RESULTS: NRIR was upregulated in AMI case and showed good diagnostic performance. Elevated NRIR levels were independently associated with poor MACE. OGD increased NRIR expression and induced cell injury, whereas NRIR knockdown alleviated apoptosis, oxidative stress, and mitochondrial dysfunction. NRIR is directly bound to miR-515-5p, which targets SLC40A1. Inhibition of miR-515-5p counteracted the effects of NRIR knockdown. Overexpression of SLC40A1 reversed the effects of miR-515-5p mimic. The NRIR/miR-515-5p/SLC40A1 axis modulated OGD-induced cardiomyocyte injury. CONCLUSIONS: NRIR is elevated in AMI, correlates with cardiac injury, and promotes cardiomyocyte damage via the miR-515-5p/SLC40A1 axis; further large-scale studies are needed to confirm its diagnostic and prognostic value.