Silencing KPNA2 Promotes Ferroptosis in Laryngeal Cancer by Activating the FoxO Signaling Pathway

We aim to clarify the specific role of Karyopherin α2 (KPNA2) in the progression of laryngeal cancer, a kind of malignant tumor with a poor curative effect. We performed the bioinformatic analysis to obtain the ferroptosis-related differentially expressed genes. KPNA2 was screened out. Then the CCK-8 assay, wound healing assay, and transwell assay were used to clarify the changes in the proliferation, migration, and invasion abilities of laryngeal cancer cells after silencing KPNA2. The concentrations of iron ions, glutathione, superoxide dismutase, and malondialdehyde were evaluated by the corresponding detection kits. The expression levels of cyclooxygenase 2, Acyl-CoA synthetase long-chain family member 4, glutathione peroxidase 4, forkhead box O (FoxO)1a and FoxO3a were determined by Western Blot. A total of 45 ferroptosis-related differentially expressed genes in laryngeal cancer were obtained, and KPNA2 was selected after bioinformatic analysis. In ferroptosis-induced laryngeal cancer cells, the cell viability, migration rate, invasion ability, and the expression of glutathione peroxidase 4, glutathione, and superoxide dismutase were further decreased and the expression of cyclooxygenase 2, Acyl-CoA synthetase long-chain family member 4, iron ions, and malondialdehyde were further increased after silencing KPNA2. The expression levels of FoxO1a and FoxO3a in laryngeal cancer cells were increased by silencing KPNA2. KPNA2 may be a promising therapeutic target for laryngeal cancer. Down-regulation of KPNA2 can promote ferroptosis in laryngeal cancer by stimulating the FoxO signaling pathway.