Wang Shuai, Yan Na, Yang Yue, Sun Li, Huang Yingxin, Zhang Jian, Xu Guangyu
Department of Infectious Disease, Changchun Infectious Disease Hospital, Changchun, China.
College of Pharmacy, Beihua University, Jilin, Jilin, China.
Front Mol Biosci. 2024 May 22;11:1410445. doi: 10.3389/fmolb.2024.1410445. eCollection 2024.
Tuberculosis is a worldwide epidemic disease, posing a serious threat to human health. To find effective drug action targets for , differentially expressed genes in tuberculosis patients and healthy people were screened by mRNA sequencing in this study. A total of 556 differentially expressed genes in tuberculosis patients and healthy people were screened out by mRNA sequencing technology. 26 transcription factors and 66 corresponding target genes were screened out in the AnimalTFDB 3.0 database, and a transcription factor regulatory network was constructed.
Three key transcription factors (TP53, KLF5 and GATA2) and one key gene (AKT1) were screened as new potential drug targets and diagnostic targets for tuberculosis by MCODE cluster analysis, and the key genes and key transcription factors were verified by RT-PCR. Finally, we constructed the and a key factor and KEGG signaling pathway regulatory network to clarify the possible molecular pathogenesis of tuberculosis.
This study suggested may activate the AKT1 gene expression by regulating transcription factors TP53, KLF5, and GATA2, thus activating the B cell receptor signaling pathway to induce the infection and invasion of . AKT1, TP53, KLF5, and GATA2 can be used as new potential drug targets for tuberculosis.
结核病是一种全球性流行病，对人类健康构成严重威胁。为了寻找有效的药物作用靶点，本研究通过mRNA测序筛选了结核病患者和健康人之间的差异表达基因。通过mRNA测序技术共筛选出556个结核病患者和健康人之间的差异表达基因。在AnimalTFDB 3.0数据库中筛选出26个转录因子和66个相应的靶基因，并构建了转录因子调控网络。
通过MCODE聚类分析筛选出三个关键转录因子（TP53、KLF5和GATA2）和一个关键基因（AKT1）作为结核病的新潜在药物靶点和诊断靶点，并通过RT-PCR对关键基因和关键转录因子进行了验证。最后，构建了关键因子和KEGG信号通路调控网络，以阐明结核病可能的分子发病机制。
本研究表明，可能通过调节转录因子TP53、KLF5和GATA2激活AKT1基因表达，从而激活B细胞受体信号通路，诱导感染和侵袭。AKT1、TP53、KLF5和GATA2可作为结核病的新潜在药物靶点。
