Document Type : Original Article
Authors
1
Celiac Disease and Gluten Related Disorders Research Center, Research Institute for Gastroenterology and Liver Disease, Shahid Beheshti University of Medical Sciences, Tehran, Iran
2
Laser Application in Medical Sciences Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
3
Skin Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
4
Cell Therapy and Regenerative Medicine Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
5
Iranian Cancer Control Center (MACSA), Tehran, Iran
6
Proteomics Research Center, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
7
Traditional Medicine and Materia Medica Research Center, School of Traditional Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
8
Clinical Tuberculosis and Epidemiology Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
9
Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
10
Diabetes Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
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.
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