Exploring Molecular Mechanism of Ferroptosis in A549 Lung Cancer Cells



Rostami Nejad M ; Razzaghi Z ; Robati R M ; Arjmand B ; Mansouri V ; Hamzeloo Moghadam M ; Rezaei M ; Bandarian F ; Razi F ; Rezaei Tavirani M
Source: Tanaffos Published:2025

Abstract

Background: Ferroptosis is a non-apoptotic cell death pattern caused by iron-dependent lipid peroxidation injury. It is a new strategy for lung cancer treatment. Molecular mechanism detection of ferroptosis via protein-protein interaction (PPI) network analysis is the main aim of this investigation. Materials and Methods: To detect gene expression changes related to ferroptosis, Gse247883 from Gene Expression Omnibus (GEO) was a candidate to be analyzed via PPI network analysis. The gene expression profiles of A549 lung cancer cells were compared with those of controls via the GEO2R program. Volcano plot visualized the significantly differentially expressed genes (DEGs). The hubs of up-and downregulated PPI networks were determined and enriched for related biological processes. Results: Some 14 hubs, including EGFR, TXNRD1, SOD1, TXN, PRDX1, PTGS2, CXCL8, TLR4, CALR, P4HB, UBC, GSR, and VCP, among the 295 recognized significant upregulated DEGs and 13 hubs; PTEN, HNRNPA1, HNRNPA2B1, HSP90AB1, NPM1, XPO1, ANLN, HNRNPC, PPP1CC, NCL, EEF1A1, HSPD1, and MATR3 for the downregulated PPI network of 249 recognized significant DEGs were determined. A total of 11 and 6 groups of various types of biological groups related to the hubs of the up-and downregulated PPI network were identified, respectively. Conclusion: In conclusion, most effects of ferroptosis are regulation of EGFR, TXNRD1, SOD1, TXN, PRDX1, PTGS2, TLR4, P4HB, UBC, GSR, VCP, PTEN, HNRNPA1, HNRNPA2B1, HSP90AB1, NPM1, XPO1, HNRNPC, NCL, EEF1A1, and HSPD1 genes and “Regulation of oxidative stress-induced cell death”, “Telomere maintenance via telomere lengthening”, and “RNA-dependent DNA biosynthetic process” groups of biological processes. © 2025 NRITLD, National Research Institute of Tuberculosis and Lung Disease, Iran.