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Identifying Hub Genes and miRNAs Associated with Mesial Temporal Lobe Epilepsy

Year 2025, Volume: 15 Issue: 2, 183 - 192, 29.08.2025
https://doi.org/10.26650/experimed.1693005

Abstract

Objective: Mesial temporal lobe epilepsy (MTLE) is a form of focal epilepsy. Recent studies indicate that microRNAs (miRNAs) are involved in the pathogenesis of MTLE. The purpose of this study was to determine differentially expressed genes (DEGs) and their regulatory miRNAs using bioinformatics analysis.

Materials and Methods: The GSE186334 gene expression dataset was retrieved from the Gene Expression Omnibus (GEO) database. DEGs between MTLE and control samples were determined using GEO2R with p<0.05 and |logFC|<−1, |logFC|>1 as the threshold. Metascape was used for functional enrichment and gene ontology (GO) analysis. Protein-protein interactions (PPIs) were generated using the STRING database and visualized with Cytoscape. The top 10 highly connected genes were identified as hub genes. Candidate miRNAs targeting these genes were predicted using the miRDB, miRWalk, TargetScan and miRNet databases.

Results: A total of 547 DEGs were found, comprising 380 upregulated and 167 downregulated genes. PPI analysis revealed 10 hub genes: IL6, IL1B, TNF, CCL2, CCL3, CCL4, CXCL8, IL1A, CD86, and CD40LG. miR-15a-5p and the hsa-let-7 family of miRNAs were predicted as potential regulators.

Conclusion: Key hub genes and regulatory miRNAs involved in MTLE were identified. The enrichment of proinflammatory genes indicates a significant role of neuroinflammation. miRNAs such as miR-15a-5p and the hsa-let-7 family may critically regulate these pathways. These insights could support the development of new diagnostic biomarkers and therapeutic strategies, pending experimental validation.

References

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  • 24. Deshmane SL, Kremlev S, Amini S, Sawaya BE. Monocyte chemoattractant protein-1 (MCP-1): An overview. J Interferon Cytokine Res 2009; 29(6): 313-26. google scholar
  • 25. Khaboushan AS, Pahlevan-Fallahy MT, Shobeiri P, Teixeira AL, Rezaei N. Cytokines and chemokines profile in encephalitis patients: A meta-analysis. PLoS One 2022; 17(9): e0273920. google scholar
  • 26. Aulickâ S, Ceskâ K, Sâna J, Siegl F, Brichtovâ E, Oslejskovâ H, et al. Cytokine-chemokine profiles in the hippocampus of patients with mesial temporal lobe epilepsy and hippocampal sclerosis. Epilepsy Res 2022; 180: 106858. google scholar
  • 27. Erta M, Quintana A, Hidalgo J. Interleukin-6, a major cytokine in the central nervous system. Int J Biol Sci 2012; 8(9): 1254-66. google scholar
  • 28. Kwack DW, Kim DW. The increased interleukin-6 levels can be an early diagnostic marker for new-onset refractory status epilepticus. J Epilepsy Res 2022; 12(2): 78-81. google scholar
  • 29. Li N, Pan J, Liu W, Li Y, Li F, Liu M. MicroRNA-15a-5p serves as a potential biomarker and regulates the viability and apoptosis of hippocampus neuron in children with temporal lobe epilepsy. Diagn Pathol 2020; 15(1): 46. google scholar
  • 30. Srivastava A, Dixit AB, Paul D, Tripathi M, Sarkar C, Chandra PS, et al. Comparative analysis of cytokine/chemokine regulatory networks in patients with hippocampal sclerosis (HS) and focal cortical dysplasia (FCD). Sci Rep 2017; 7(1): 15904. google scholar

Year 2025, Volume: 15 Issue: 2, 183 - 192, 29.08.2025
https://doi.org/10.26650/experimed.1693005

Abstract

References

  • 1. William C. McIntosh, Joe M. Das. Temporal Seizure. In: StatPearls. 2023. google scholar
  • 2. Baulac M. MTLE with hippocampal sclerosis in adult as a syndrome. Rev Neurol 2015; 171(3): 259-66. google scholar
  • 3. Liu C, Qiao XZ, Wei ZH, Cao M, Wu ZY, Deng YC. Molecular typing of familial temporal lobe epilepsy. World J Psychiatry 2022; 12(1): 98-107. google scholar
  • 4. Hedera P, Blair MA, Andermann E, Andermann F, D’agostino D, Taylor KA, et al. Familial mesial temporal lobe epilepsy maps to chromosome 4q13.2-q21.3. Neurology 2007; 68(24): 2107-12. google scholar
  • 5. Maurer-Morelli C V., Secolin R, Morita ME, Domingues RR, Marchesini RB, Santos NF, et al. A locus identified on chromosome18p11.31 is associated with hippocampal abnormalities in a family with mesial temporal lobe epilepsy. Front Neurol 2012; 3: 124. google scholar
  • 6. Leal B, Chaves J, Carvalho C, Rangel R, Santos A, Bettencourt A, et al. Brain expression of inflammatory mediators in Mesial Temporal Lobe Epilepsy patients. J Neuroimmunol 2017; 313: 82-8. google scholar
  • 7. Ruffolo G, Martinello K, Labate A, Cifelli P, Fucile S, Di Gennaro G, et al. Modulation of GABAergic dysfunction due to SCN1A mutation linked to Hippocampal Sclerosis. Ann Clin Transl Neurol 2020; 7(9): 1726-31. google scholar
  • 8. Silvennoinen K, Gawel K, Tsortouktzidis D, Pitsch J, Alhusaini S, van Loo KMJ, et al. SCN1A overexpression, associated with a genomic region marked by a risk variant for a common epilepsy, raises seizure susceptibility. Acta Neuropathol 2022; 144(1): 107-27. google scholar
  • 9. Gurses C, Azakli H, Alptekin A, Cakiris A, Abaci N, Arikan M, et al. Mitochondrial DNA profiling via genomic analysis in mesial temporal lobe epilepsy patients with hippocampal sclerosis. Gene 2014; 538(2): 323-7. google scholar
  • 10. Yang M, Li Y, Liu X, Zou S, Lei L, Zou Q, et al. Autophagy-related genes in mesial temporal lobe epilepsy: an integrated bioinformatics analysis. Acta Epileptol 2024; 6(1): 16. google scholar
  • 11. Martinez B, Peplow P V. MicroRNAs as potential biomarkers in temporal lobe epilepsy and mesial temporal lobe epilepsy. Neural Regen Res 2023; 18(4): 71626. google scholar
  • 12. Pagni S, Mills JD, Frankish A, Mudge JM, Sisodiya SM. Non-coding regulatory elements: Potential roles in disease and the case of epilepsy. Neuropathology Appl Neurobiol 2022; 48(3): e12775. google scholar
  • 13. Zhukova JV, Lopatnikova JA, Alshevskaya AA, Sennikov SV. Molecular mechanisms of regulation of IL-1 and its receptors. Cytokine Growth Factor Rev 2024; 80: 59-71. google scholar
  • 14. Kang H, Dong Y, Peng R, Liu H, Guo Q, Song K, et al. Inhibition of IRE1 suppresses the catabolic effect of IL-1B on nucleus pulposus celi and prevents intervertebral disc degeneration in vivo. Biochem Pharmacol 2022; 197: 114932. google scholar
  • 15. Saghazadeh A, Gharedaghi M, Meysamie A, Bauer S, Rezaei N. Proinflammatory and anti-inflammatory cytokines in febrile seizures and epilepsy: Systematic review and meta-analysis. Rev Neurosci 2014; 25(2): 281-305. google scholar
  • 16. Mu J, Cao C, Gong Y, Hu G. Relationship between inflammation/immunity and epilepsy: A multi-omics mendelian randomization study integrating GWAS, eQTL, and mQTL data. Epilepsy and Behavior 2024; 161. google scholar
  • 17. Uludağ IF, Duksal T, Tiftikcioglu Bl, Zorlu Y, Ozkaya F, Kirkali G. IL-lp, IL-6 and IL1Ra levels in temporal lobe epilepsy. Seizure 2015; 26: 22-5. google scholar
  • 18. Strauss KI, Elisevich KV. Brain region and epilepsy-associated differences in inflammatory mediator levels in medically refractory mesial temporal lobe epilepsy. J Neuroinflammation 2016; 13(1): 270. google scholar
  • 19. Pototskiy E, Vinokuroff K, Ojeda A, Major CK, Sharma D, Anderson T, et al. Downregulation of CD40L-CD40 attenuates seizure susceptibility and severity of seizures. Sci Rep 2021; 11(1): 17262. google scholar
  • 20. Gonzalez Caldito N. Role of tumor necrosis factor-alpha in the central nervous system: a focus on autoimmune disorders. Front Immunol 2023; 14: 1213448. google scholar
  • 21. Casillas-Espinosa PM, Powell KL, O’Brien TJ. Regulators of synaptic transmission: roles in the pathogenesis and treatment of epilepsy. Epilepsia 2012; 53(9): 41-58. google scholar
  • 22. Patel DC, Wallis G, Jill Dahle E, McElroy PB, Thomson KE, Tesi RJ, et al. Hippocampal TNFa signaling contributes to seizure generation in an infection-induced mouse model of limbic epilepsy. eNeuro 2017; 4(2): ENEURO.0105-17.2017. google scholar
  • 23. Ashhab MU, Omran A, Kong H, Gan N, He F, Peng J, et al. Expressions of tumor necrosis factor alpha and MicroRNA-155 in immature rat model of status epilepticus and children with mesial temporal lobe epilepsy. J Mol Neurosci 2013; 51(3): 950-8. google scholar
  • 24. Deshmane SL, Kremlev S, Amini S, Sawaya BE. Monocyte chemoattractant protein-1 (MCP-1): An overview. J Interferon Cytokine Res 2009; 29(6): 313-26. google scholar
  • 25. Khaboushan AS, Pahlevan-Fallahy MT, Shobeiri P, Teixeira AL, Rezaei N. Cytokines and chemokines profile in encephalitis patients: A meta-analysis. PLoS One 2022; 17(9): e0273920. google scholar
  • 26. Aulickâ S, Ceskâ K, Sâna J, Siegl F, Brichtovâ E, Oslejskovâ H, et al. Cytokine-chemokine profiles in the hippocampus of patients with mesial temporal lobe epilepsy and hippocampal sclerosis. Epilepsy Res 2022; 180: 106858. google scholar
  • 27. Erta M, Quintana A, Hidalgo J. Interleukin-6, a major cytokine in the central nervous system. Int J Biol Sci 2012; 8(9): 1254-66. google scholar
  • 28. Kwack DW, Kim DW. The increased interleukin-6 levels can be an early diagnostic marker for new-onset refractory status epilepticus. J Epilepsy Res 2022; 12(2): 78-81. google scholar
  • 29. Li N, Pan J, Liu W, Li Y, Li F, Liu M. MicroRNA-15a-5p serves as a potential biomarker and regulates the viability and apoptosis of hippocampus neuron in children with temporal lobe epilepsy. Diagn Pathol 2020; 15(1): 46. google scholar
  • 30. Srivastava A, Dixit AB, Paul D, Tripathi M, Sarkar C, Chandra PS, et al. Comparative analysis of cytokine/chemokine regulatory networks in patients with hippocampal sclerosis (HS) and focal cortical dysplasia (FCD). Sci Rep 2017; 7(1): 15904. google scholar
There are 30 citations in total.

Details

Primary Language English
Subjects Clinical Sciences (Other)
Journal Section Research Article
Authors

Simay Bozkurt 0000-0002-9185-4225

Ömer Faruk Düzenli 0000-0002-2938-711X

Emrah Yücesan 0000-0003-4512-8764

Publication Date August 29, 2025
Submission Date May 6, 2025
Acceptance Date June 24, 2025
Published in Issue Year 2025 Volume: 15 Issue: 2

Cite

Vancouver Bozkurt S, Düzenli ÖF, Yücesan E. Identifying Hub Genes and miRNAs Associated with Mesial Temporal Lobe Epilepsy. Experimed. 2025;15(2):183-92.