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铁死亡相关基因在类风湿性关节炎中的作用机制

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目的 基于生物信息学和网络药理学探讨铁死亡相关基因在类风湿性关节炎(RA)中的作用机制.方法 从基因表达综合数据库中获得RA的数据集,从FerrDb数据库下载铁死亡相关基因.分析RA患者和正常对照中的差异表达基因,将其与铁死亡相关基因取交集,获得铁死亡相关差异表达基因(FRDEGs).对FRDEGs进行基因本体论功能富集分析、京都基因与基因组百科全书信号通路富集分析和蛋白互作网络(PPI)分析,使用CytoHubba插件筛选关键基因.绘制ROC曲线验证关键基因预测RA的效能.使用CoreMine在线数据库分析预测相关中药,对关键基因的靶标蛋白与中药有效成分进行分子对接.结果 共筛选出18个FRDEGs,主要富集在细胞增殖和免疫相关反应通路.PPI分析得到7个关键基因,其中周期蛋白依赖性激酶抑制剂(CDKN1A)基因、双特异性磷酸酶1(DUSP1)基因和丝裂原活化蛋白激酶(MAPK)8等3个关键基因诊断RA的AUC分别为0.875、0.812和0.804,可作为RA的诊断标志物.分子对接结果表明,来自姜黄、黄芩和灵芝的主要成分豆甾醇、β-谷甾醇和(4R)-4-戊酸与关键基因结合稳定,其中β-谷甾醇与CDKNA1的对接结合能最低.结论 基于生物信息学和网络药理学分析得到CDKN1A、DUSP1和MAPK8等3个治疗RA的潜在关键生物标志物和治疗靶点,为后续研究铁死亡相关基因在RA中的作用机制提供了理论基础.
Analysis of ferroptosis-related genes in rheumatoid arthritis:a study based on bioinformatics and network pharmacology
Objective To analyze the ferroptosis-related genes in rheumatoid arthritis (RA) based on bioinformatics and network pharmacology.Methods RA datasets were obtained from the Gene Expression Omnibus database,the dataset of ferroptosis-related genes was downloaded from FerrDb database.Differentially expressed genes between RA patients and healthy subjects were analysed,and ferroptosis-related differentially expressed genes (FRDEGs) were obtained.Gene ontology functional enrichment analysis,Kyoto encyclopedia of genes and genomes signalling pathway enrichment analysis and protein-protein interaction network (PPI) analysis were performed on FRDEGs.Key genes were screened using the CytoHubba plugin.The diagnostic ability of key genes to predict RA was evaluated with ROC curve.The relevant Chinese medicines were predicted using CoreMine online database,and the target proteins of key genes were molecularly docked with the active ingredients of Chinese medicines.Results A total of 18 FRDEGs were screened out,which were mainly enriched in cell proliferation and immune-related response pathways.PPI analysis obtained 7 key genes,among which cyclin-dependent kinase inhibitor 1A (CDKN1A) gene,dual-specificity phosphatase 1 (DUSP1) gene and mitogen-activated protein kinase (MAPK) 8,had AUCs of 0.875,0.812,and 0.804,respectively.The molecular docking results showed that the major components leguminol,β-sitosterol and (4R)-4-pentanoic acids from Turmeric,Scutellaria baicalensis and Ganoderma lucidum were bound stably to the key genes,with β-sitosterol having the lowest docking binding energy to CDKNA1.Conclusion Three potential key biomarkers and therapeutic targets for the treatment of RA,including CDKN1A,DUSP1 and MAPK8 have been identified based on bioinformatics and network pharmacology analysis,which provides reference for subsequent studies on the mechanism of ferroptosis-related genes in RA.

Ferroptosis-related genesRheumatoid arthritisBioinformaticsNetwork pharmacology

李玉杰、吴巧萍、李情操、赵荣青

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315046 宁波市医疗中心李惠利医院检验科

铁死亡相关基因 类风湿性关节炎 生物信息学 网络药理学

2024

浙江医学
浙江省医学会

浙江医学

CSTPCD
影响因子:0.428
ISSN:1006-2785
年,卷(期):2024.46(24)