Bioinformatics-based Analysis of Key Genes Linking Mitophagy and Feroptosis in Ischemic Stroke

doi:10.3870/j.issn.1672-0741.25.07.042

Abstract

Abstract: Objective To investigate key genes associated with mitophagy and ferroptosis in ischemic stroke(IS)and explore their relationship. Methods Gene expression profiles related to IS were obtained from the Gene Expression Omnibus(GEO),GeneCards,and ferroptosis-related databases.Commonly differentially expressed genes(co-DEGs)were identified,subjecting to functional enrichment and protein-protein interaction(PPI)network analyses.Topological algorithms were applied to screen potential candidate genes,whose diagnostic performance was evaluated by receiver operating characteristic(ROC)curve analysis.The identified target genes were further validated using independent disease-related datasets and animal experiments.Sprague-Dawley (SD)rats were randomly divided into sham(n=10)and model(n=10)groups.Western blotting and quantitative real-time PCR(qRT-PCR)were performed to assess gene expression levels. Results A total of 36 shared genes were identified,which were significantly enriched in pathways associated with autophagy and ferroptosis.Among them,SIRT3,STAT3,HMOX1,and NFE2L2 were identified as key targets.In IS,SIRT3 expression was markedly decreased(P<0.05),whereas STAT3,HMOX1,and NFE2L2 were significantly upregulated(P<0.05).ROC curve analysis yielded area under the curve(AUC)values of 1.0 for all four target genes.Consistent with the bioinformatics findings,animal experiments confirmed increased protein levels of STAT3,HMOX1,and NFE2L2,and decreased SIRT3 in the model group(P<0.05). Conclusion SIRT3,STAT3,HMOX1,and NFE2L2 may serve as critical genes linking mitophagy,ferroptosis,and IS pathogenesis.

Key words: ischemic stroke, mitophagy, bioinformatics, ferroptosis, reactive oxygen species

CLC Number:

R743.3

Huang Mengling, Li Ruiqing, Huang Jin et al. Bioinformatics-based Analysis of Key Genes Linking Mitophagy and Feroptosis in Ischemic Stroke[J]. Acta Medicinae Universitatis Scientiae et Technologiae Huazhong, 2026, 55(2): 164-174.

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