Identifying disulfidptosis-related biomarkers in epilepsy based on integrated bioinformatics and experimental analyses
One of the underlying mechanisms of epilepsy (EP), a brain disease characterized by recurrent seizures, is considered to be cell death. Disulfidptosis, a proposed novel cell death mechanism, is thought to play a part in the pathogenesis of epilepsy, but the exact role is unclear. The gene expression...
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Elsevier
2025-02-01
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| Series: | Neurobiology of Disease |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996125000051 |
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| author | Sijun Li Lanfeng Sun Hongmi Huang Xing Wei Yuling Lu Kai Qian Yuan Wu |
| author_facet | Sijun Li Lanfeng Sun Hongmi Huang Xing Wei Yuling Lu Kai Qian Yuan Wu |
| author_sort | Sijun Li |
| collection | DOAJ |
| description | One of the underlying mechanisms of epilepsy (EP), a brain disease characterized by recurrent seizures, is considered to be cell death. Disulfidptosis, a proposed novel cell death mechanism, is thought to play a part in the pathogenesis of epilepsy, but the exact role is unclear. The gene expression omnibus series (GSE) 33000 and GSE63808 datasets were used to search for differentially expressed disulfidptosis-related molecules (DE-DRMs). A correlation between the DE-DRMs was discovered. Individuals with epilepsy were then used to investigate molecular clusters based on the expression of DE-DRMs. Following that, the best machine learning model which is validated by GSE143272 dataset and predictor molecules were identified. The correlation between predictive molecules and clinical traits was determined. Based on the in vitro and in vivo seizures models, experimental analyses were applied to verify the DE-DRMs expressions and the correlation between them. Nine molecules were identified as DE-DRMs: glycogen synthase 1 (GYS1), solute carrier family 3 member 2 (SLC3A2), solute carrier family 7 member 11 (SLC7A11), NADH:ubiquinone oxidoreductase core subunit S1 (NDUFS1), 3-oxoacyl-ACP synthase, mitochondrial (OXSM), leucine rich pentatricopeptide repeat containing (LRPPRC), NADH:ubiquinone oxidoreductase subunit A11 (NDUFA11), NUBP iron‑sulfur cluster assembly factor, mitochondrial (NUBPL), and NCK associated protein 1 (NCKAP1). NDUFS1 interacted with NDUFA11, NUBPL, and LRPPRC, while SLC3A2 interacted with SLC7A11. The optimal machine learning model was revealed to be the random forest (RF) model. G protein guanine nucleotide-binding protein alpha subunit q (GNAQ) was linked to sodium valproate resistance. The experimental analyses suggested an upregulated SLC7A11 expression, an increased number of formed SLC3A2 and SLC7A11 complexes, and a decreased number of formed NDUFS1 and NDUFA11 complexes. This study provides previously undocumented evidence of the relationship between disulfidptosis and EP. In addition to suggesting that SLC7A11 may be a specific DRM for EP, this research demonstrates the alterations in two disulfidptosis-related protein complexes: SLC7A11-SLC3A2 and NDUFS1-NDUFA11. |
| format | Article |
| id | doaj-art-d2ff90df37e84a84bbe21dac85f256bd |
| institution | Kabale University |
| issn | 1095-953X |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
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| series | Neurobiology of Disease |
| spelling | doaj-art-d2ff90df37e84a84bbe21dac85f256bd2025-01-24T04:44:40ZengElsevierNeurobiology of Disease1095-953X2025-02-01205106789Identifying disulfidptosis-related biomarkers in epilepsy based on integrated bioinformatics and experimental analysesSijun Li0Lanfeng Sun1Hongmi Huang2Xing Wei3Yuling Lu4Kai Qian5Yuan Wu6Department of Neurology, the First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, Nanning, Guangxi, ChinaDepartment of Neurology, the First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, Nanning, Guangxi, ChinaDepartment of Neurology, the First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, Nanning, Guangxi, ChinaDepartment of Neurology, the First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, Nanning, Guangxi, ChinaDepartment of Neurology, the First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, Nanning, Guangxi, ChinaDepartment of Neurology, the First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, Nanning, Guangxi, ChinaCorresponding author.; Department of Neurology, the First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, Nanning, Guangxi, ChinaOne of the underlying mechanisms of epilepsy (EP), a brain disease characterized by recurrent seizures, is considered to be cell death. Disulfidptosis, a proposed novel cell death mechanism, is thought to play a part in the pathogenesis of epilepsy, but the exact role is unclear. The gene expression omnibus series (GSE) 33000 and GSE63808 datasets were used to search for differentially expressed disulfidptosis-related molecules (DE-DRMs). A correlation between the DE-DRMs was discovered. Individuals with epilepsy were then used to investigate molecular clusters based on the expression of DE-DRMs. Following that, the best machine learning model which is validated by GSE143272 dataset and predictor molecules were identified. The correlation between predictive molecules and clinical traits was determined. Based on the in vitro and in vivo seizures models, experimental analyses were applied to verify the DE-DRMs expressions and the correlation between them. Nine molecules were identified as DE-DRMs: glycogen synthase 1 (GYS1), solute carrier family 3 member 2 (SLC3A2), solute carrier family 7 member 11 (SLC7A11), NADH:ubiquinone oxidoreductase core subunit S1 (NDUFS1), 3-oxoacyl-ACP synthase, mitochondrial (OXSM), leucine rich pentatricopeptide repeat containing (LRPPRC), NADH:ubiquinone oxidoreductase subunit A11 (NDUFA11), NUBP iron‑sulfur cluster assembly factor, mitochondrial (NUBPL), and NCK associated protein 1 (NCKAP1). NDUFS1 interacted with NDUFA11, NUBPL, and LRPPRC, while SLC3A2 interacted with SLC7A11. The optimal machine learning model was revealed to be the random forest (RF) model. G protein guanine nucleotide-binding protein alpha subunit q (GNAQ) was linked to sodium valproate resistance. The experimental analyses suggested an upregulated SLC7A11 expression, an increased number of formed SLC3A2 and SLC7A11 complexes, and a decreased number of formed NDUFS1 and NDUFA11 complexes. This study provides previously undocumented evidence of the relationship between disulfidptosis and EP. In addition to suggesting that SLC7A11 may be a specific DRM for EP, this research demonstrates the alterations in two disulfidptosis-related protein complexes: SLC7A11-SLC3A2 and NDUFS1-NDUFA11.http://www.sciencedirect.com/science/article/pii/S0969996125000051EpilepsySeizuresDisulfidptosis-related moleculesSLC7A11Protein complexes |
| spellingShingle | Sijun Li Lanfeng Sun Hongmi Huang Xing Wei Yuling Lu Kai Qian Yuan Wu Identifying disulfidptosis-related biomarkers in epilepsy based on integrated bioinformatics and experimental analyses Neurobiology of Disease Epilepsy Seizures Disulfidptosis-related molecules SLC7A11 Protein complexes |
| title | Identifying disulfidptosis-related biomarkers in epilepsy based on integrated bioinformatics and experimental analyses |
| title_full | Identifying disulfidptosis-related biomarkers in epilepsy based on integrated bioinformatics and experimental analyses |
| title_fullStr | Identifying disulfidptosis-related biomarkers in epilepsy based on integrated bioinformatics and experimental analyses |
| title_full_unstemmed | Identifying disulfidptosis-related biomarkers in epilepsy based on integrated bioinformatics and experimental analyses |
| title_short | Identifying disulfidptosis-related biomarkers in epilepsy based on integrated bioinformatics and experimental analyses |
| title_sort | identifying disulfidptosis related biomarkers in epilepsy based on integrated bioinformatics and experimental analyses |
| topic | Epilepsy Seizures Disulfidptosis-related molecules SLC7A11 Protein complexes |
| url | http://www.sciencedirect.com/science/article/pii/S0969996125000051 |
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