摘要
目的 基于生物信息学探讨线粒体功能障碍导致白癜风的机制研究.方法 从CTD/Gene-Cards/OMIM/NCBI Gene数据库获取白癜风靶基因取并集,MITOMAP数据库下载线粒体功能障碍靶基因,进行交集分析筛选出共同基因;通过蛋白质互作分析筛选出核心基因;对共同基因进行GO、KEGG富集分析;并使用NetworkAnalyst、Toppgene数据库预测核心基因相关的转录因子、miRNA和药物.结果 白癜风与线粒体功能障碍共有90个共同基因,通过蛋白质互作筛选出13个核心基因.共同基因的生物过程主要富集在线粒体呼吸链复合体组装等,细胞组分主要富集在线粒体;分子功能主要富集在为氧化还原驱动的跨膜转运蛋白活性、氧化还原酶活性等.KEGG主要富集呼吸电子传输等;与核心基因互作度高的转录因子有ATF1、KDM5A、KDM5B、PHF8、SAP30等,与核心基因互作度高的miRNA有hsa-mir-1-3p、hsa-mir-16-5p,预测药物包括硫辛酸和辅酶Q10等.结论 线粒体功能障碍可能通过影响线粒体呼吸链中复合体组装、电子传输等生物过程促使白癜风发病;ATF1、KDM5等转录因子和miR-1、miR493 等 miRNA 可能通过与关键基因 NDUFA9、SURF1、NDUFS1、NDUFS4、LRPPRC 相互作用在白癜风发病过程中发挥重要作用.
Abstract
Objective To investigate the mechanisms of mitochondrial dysfunction-induced vitiligo based on bioinformatics.Methods The vitiligo target genes were obtained from CTD/Gene Cards/OMIM/NCBI Gene databases,while mitochondrial dysfunction target genes were download-ed from the MITOMAP database,followed by intersection analysis to identify the common genes.The latter were subjected to GO and KEGG enrichment analysis.The core genes were screened by analysis of protein-protein interaction.The Network Analyst and Toppgene databases were used to predict the core gene-related transcription factors,miRNAs and the treatments.Results There were 90 common genes in vitiligo and mitochondrial dysfunction,and 13 core genes were screened by analysis of protein-protein interaction.The biological processes of the common genes were mainly enriched in mitochondrial respiratory chain complex assembly,while the cellular compo-nents were mainly enriched in mitochondria.The molecular functions were mainly enriched in the activities of redox-driven transmembrane transporter and oxidoreductase,and KEGG was mainly enriched in respiratory electron transport.The transcription factors with high degree of interactions with the core genes included ATF1,KDM5A,KDM5B and PHF8,and the miRNAs with high in-teraction with core genes included hsa-mir-1-3p and hsa-mir-16-5p.The predicted effective drugs were lipoic acid and ubiquinols.Conclusions Mitochondrial dysfunction may contribute to patho-genesis of vitiligo by affecting biological processes,such as complex assembly and electron trans-port in the mitochondrial respiratory chain.Transcription factors,such as ATF1 and KDM5,and miRNAs,including miR-1 and miR-493,may play an important pathogenic role in vitiligo by in-teraction with key genes,such as NDUFA9,SURF1,NDUFS1,NDUFS4 and LRPPRC.
国家科技期刊平台
NSTL
维普
万方数据