基于GEO数据库和转录因子调控网络的结核病药物作用靶点筛选及其作用机制  

Screening of Tuberculosis Drug Targets and Their Mechanism Based on GEO Database and Transcription Factor Regulatory Network

作　　者：赵悦含 杨悦 徐广宇[1] ZHAO Yuehan;YANG Yue;XU Guangyu(School of Pharmacy,Beihua University,Jilin 132013,China)

机构地区：[1]北华大学药学院,吉林吉林132013

出　　处：《北华大学学报（自然科学版）》2024年第3期346-353,共8页Journal of Beihua University（Natural Science）

基　　金：国家自然科学基金项目(81973371)。

摘　　要：目的基于GEO数据库和转录因子调控网络筛选抗结核病药物及药物作用靶点。方法通过NCBI的GEO数据库,筛选结核病患者和健康者之间差异表达的基因;通过AnimalTFDB 3.0数据库预测差异表达基因中的转录因子,并构建转录因子调控网络;通过调控网络中的关键基因筛选相关miRNA,并筛选关键节点,初步阐明结核病致病的分子机制。结果通过GEO数据库检索,筛选出的差异表达基因为784个;通过AnimalTFDB 3.0数据库筛选出23个转录因子和对应的790个靶基因,构建了转录因子-靶基因的调控网络;通过TargetScanHuman 7.2查询到关键节点对应的miRNA,构建“转录因子-靶基因-miRNA”调控网络,筛选出4个结核病药物靶点(EP300,CREBBP,ELAVL1,HSP90AA1),阐明了其与转录因子和miRNA之间的调控机制。结论通过构建结核“转录因子-靶基因-miRNA”网络,筛选出结核病新的潜在药物作用靶点——EP300、CREBBP、ELAVL1、HSP90AA1;同时发现,EP300、CREBBP、HSP90AA1通过激活转录因子STAT2,导致机体内炎症因子TNF-α水平增高,进而抑制了miR-9-5p的表达;而基因ELAVL1直接抑制miR-9-5p的表达,并且与NOD-like receptor signaling pathay通路密切相关,导致结核病的发生发展。Objective To screen anti-tuberculosis drugs and drug targets based on GEO database and transc-ription factor regulatory network.Method To screen differentially expressed genes between TB patients and healthy people through NCBI GEO database.To predict transcription factors in differentially expressed genes through AnimalTFDB 3.0 database,and to construct transcription factor regulatory network and finally to screen related miRNAs through key genes in the regulatory network and to screen key nodes to elucidate initially the molecular mechanism of TB pathogenesis.Results 784 differentially expressed genes were screened through GEO database search.23 transcription factors and the corresponding 790 target genes were screened through AnimalTFDB 3.0 database and the transcription factor-target gene regulatory network was constructed.The miRNAs corresponding to the key nodes were queried through TargetScanHuman 7.2,and the transcription factor-target gene-miRNA regulatory network was constructed to screen four TB drug targets(EP300,CREBBP,ELAVL1,HSP90AA1)and elucidated the regulatory mechanisms between the transcription factors and miRNA.Conclusion The new potential drug targets for TB were screened(EP300,CREBBP,ELAVL1,HSP90AA1),the transcription factors STAT2 can be activated to increase the level of TNF-αand inhibit the expression of miR-9-5p,and are closely related with NOD-like receptor signaling pathway,the pathogenic process of TB were elucidated.

关 键 词：结核病 药物靶点 GEO数据库 转录因子 调控网络 

分 类 号：R994.6[医药卫生—毒理学]