Identification of Ferroptosis-related Genes in Acute Phase of Temporal Lobe Epilepsy Based on Bioinformatic Analysis

Overview

Journal BMC Genomics

Publisher Biomed Central

Specialty Genetics

Date 2023 Nov 9

PMID 37946105

Authors

Shihao Chen

Xing Jin

Tao He

Mulan Zhang

Huiqin Xu

Affiliations

Soon will be listed here.

Abstract

Background: Epilepsy is a prevalent neurological disorder, and while its precise mechanism remains elusive, a connection to ferroptosis has been established. This study investigates the potential clinical diagnostic significance of ferroptosis-related genes (FRGs) during the acute phase of temporal lobe epilepsy.

Methods: To identify differentially expressed genes (DEGs), we accessed data from the GEO database and performed an intersection analysis with the FerrDB database to pinpoint FRGs. A protein-protein interaction (PPI) network was constructed. To assess the diagnostic utility of the discovered feature genes for the disease, ROC curve analysis was conducted. Subsequently, qRT-PCR was employed to validate the expression levels of these feature genes.

Results: This study identified a total of 25 FRGs. PPI network analysis revealed six feature genes: IL6, PTGS2, HMOX1, NFE2L2, TLR4, and JUN. ROC curve analysis demonstrated that the combination of these six feature genes exhibited the highest diagnostic potential. qRT-PCR validation confirmed the expression of these feature genes.

Conclusion: We have identified six feature genes (IL6, PTGS2, HMOX1, NFE2L2, TLR4, and JUN) strongly associated with ferroptosis in epilepsy, suggesting their potential as biomarkers for the diagnosis of temporal lobe epilepsy.

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References

Roggenhofer E, Toumpouli E, Seeck M, Wiest R, Lutti A, Kherif F . Clinical phenotype modulates brain's myelin and iron content in temporal lobe epilepsy. Brain Struct Funct. 2021; 227(3):901-911. PMC: 8930791. DOI: 10.1007/s00429-021-02428-z. View

Kummer K, Zeidler M, Kalpachidou T, Kress M . Role of IL-6 in the regulation of neuronal development, survival and function. Cytokine. 2021; 144:155582. DOI: 10.1016/j.cyto.2021.155582. View

Xie R, Zhao W, Lowe S, Bentley R, Hu G, Mei H . Quercetin alleviates kainic acid-induced seizure by inhibiting the Nrf2-mediated ferroptosis pathway. Free Radic Biol Med. 2022; 191:212-226. DOI: 10.1016/j.freeradbiomed.2022.09.001. View

Meng Q, Xia Y . c-Jun, at the crossroad of the signaling network. Protein Cell. 2011; 2(11):889-98. PMC: 4875184. DOI: 10.1007/s13238-011-1113-3. View

An Y, Luo Q, Han D, Guan L . Abietic acid inhibits acetaminophen-induced liver injury by alleviating inflammation and ferroptosis through regulating Nrf2/HO-1 axis. Int Immunopharmacol. 2023; 118:110029. DOI: 10.1016/j.intimp.2023.110029. View

Thiruvengadam M, Venkidasamy B, Subramanian U, Samynathan R, Shariati M, Rebezov M . Bioactive Compounds in Oxidative Stress-Mediated Diseases: Targeting the NRF2/ARE Signaling Pathway and Epigenetic Regulation. Antioxidants (Basel). 2021; 10(12). PMC: 8698417. DOI: 10.3390/antiox10121859. View

Kalozoumi G, Kel-Margoulis O, Vafiadaki E, Greenberg D, Bernard H, Soreq H . Glial responses during epileptogenesis in Mus musculus point to potential therapeutic targets. PLoS One. 2018; 13(8):e0201742. PMC: 6095496. DOI: 10.1371/journal.pone.0201742. View

Wang L, Duan C, Wang R, Chen L, Wang Y . Inflammation-related genes and immune infiltration landscape identified in kainite-induced temporal lobe epilepsy based on integrated bioinformatics analysis. Front Neurosci. 2022; 16:996368. PMC: 9648357. DOI: 10.3389/fnins.2022.996368. View

Zhou Q, Wang Q, He B, Kong H, Luo H, Wang X . MicroRNA 322-5p reduced neuronal inflammation via the TLR4/TRAF6/NF-κB axis in a rat epilepsy model. Open Med (Wars). 2022; 17(1):907-914. PMC: 9106113. DOI: 10.1515/med-2022-0485. View

10.

Jiang Y, Yang X, Duan D, Zhang Y, Li N, Tang L . Inhibition of MALT1 reduces ferroptosis in rat hearts following ischemia/reperfusion via enhancing the Nrf2/SLC7A11 pathway. Eur J Pharmacol. 2023; 950:175774. DOI: 10.1016/j.ejphar.2023.175774. View

11.

Anandhan A, Dodson M, Shakya A, Chen J, Liu P, Wei Y . NRF2 controls iron homeostasis and ferroptosis through HERC2 and VAMP8. Sci Adv. 2023; 9(5):eade9585. PMC: 9891695. DOI: 10.1126/sciadv.ade9585. View

12.

Chong D, Jones N, Schittenhelm R, Anderson A, Casillas-Espinosa P . Multi-omics integration and epilepsy: Towards a better understanding of biological mechanisms. Prog Neurobiol. 2023; 227:102480. DOI: 10.1016/j.pneurobio.2023.102480. View

13.

Liang Y, Liu Z, Qu L, Wang Y, Zhou Y, Liang L . Inhibition of the IRE1/JNK pathway in renal tubular epithelial cells attenuates ferroptosis in acute kidney injury. Front Pharmacol. 2022; 13:927641. PMC: 9461286. DOI: 10.3389/fphar.2022.927641. View

14.

Liu J, Kang R, Tang D . Signaling pathways and defense mechanisms of ferroptosis. FEBS J. 2021; 289(22):7038-7050. DOI: 10.1111/febs.16059. View

15.

Cai Y, Yang Z . Ferroptosis and Its Role in Epilepsy. Front Cell Neurosci. 2021; 15:696889. PMC: 8319604. DOI: 10.3389/fncel.2021.696889. View

16.

Kanehisa M, Furumichi M, Sato Y, Kawashima M, Ishiguro-Watanabe M . KEGG for taxonomy-based analysis of pathways and genomes. Nucleic Acids Res. 2022; 51(D1):D587-D592. PMC: 9825424. DOI: 10.1093/nar/gkac963. View

17.

Song X, Long D . Nrf2 and Ferroptosis: A New Research Direction for Neurodegenerative Diseases. Front Neurosci. 2020; 14:267. PMC: 7186402. DOI: 10.3389/fnins.2020.00267. View

18.

Ferrer M, Busquets-Cortes C, Capo X, Tejada S, Tur J, Pons A . Cyclooxygenase-2 Inhibitors as a Therapeutic Target in Inflammatory Diseases. Curr Med Chem. 2018; 26(18):3225-3241. DOI: 10.2174/0929867325666180514112124. View

19.

Hirano T, Hirayama D, Wagatsuma K, Yamakawa T, Yokoyama Y, Nakase H . Immunological Mechanisms in Inflammation-Associated Colon Carcinogenesis. Int J Mol Sci. 2020; 21(9). PMC: 7247693. DOI: 10.3390/ijms21093062. View

20.

Ni S, Yuan Y, Song S, Li X . A double-edged sword with a therapeutic target: iron and ferroptosis in immune regulation. Nutr Rev. 2022; 81(5):587-596. DOI: 10.1093/nutrit/nuac071. View