AURKA Induces Ferroptosis Via Keap1/NRF2/HO-1 Signaling Pathway in EGFR Mutated Lung Adenocarcinoma

Lung adenocarcinoma (LUAD) is a leading cause of cancer-related deaths worldwide. Despite the availability of targeted therapies, the mortality rate remains high. Our study explores the role of Aurora kinase A (AURKA) in the progression of LUAD and its potential as a new therapeutic target.Through bioinformatics analysis and experimental validation in H1975 cells, we have uncovered AURKA's significant association with LUAD prognosis, EGFR mutations, and immune cell infiltration. We found that reducing AURKA expression can inhibit cell migration and induce cell cycle arrest, as well as enhance pathways related to ferroptosis---a form of regulated cell death.Our research indicates that AURKA regulates ferroptosis via the Keap1-NRF2-HO-1 pathway, which is crucial for maintaining cellular iron balance and managing lipid peroxidation. Additionally, we discovered that AURKA downregulation promotes the nuclear translocation of NRF2 and increases the expression of heme oxygenase-1 (HO-1), effects that can be reversed by the NRF2 inhibitor ML385.These findings highlight AURKA's importance as a potential biomarker for LUAD and its role in modulating ferroptosis. Our work provides valuable insights into the pathogenesis of LUAD and may contribute to the development of novel, targeted anti-tumor therapies.