PD-1与其他蛋白质的互作网络分析及验证

摘要

Objective An interaction network among PD-1-ligands and other proteins were built to add deeper understanding of PD-1 signal pathway and to supply the theoretical data on the clinical application study of PD-1 and its ligands.Methods Searching the literature about PD-1 and its ligands in the PubMed,the result of which would be used to summarize the proteins that had been reported to have interactions with PD-1 and its ligands,and then,quadratic search would be performed on these proteins.Finally,the software Cytoscape would be used to build and analyze the interaction network and verified by PCR.Results There were 122 and 126 nodes in the PD-1/PD-L1 network and PD-1/PD-L2 network respectively.These proteins were involved in TCR signal path-way,cell adhesion,JAK-STAT signal pathway and interaction between cytokines.Meanwhile,a perspective that PD-L1 may influ-ence on CXCR4 through JAK-STAT pathway based on the network which had been supported by qPCR.Conclusion The bioinfor-matics suggested that there are differences between the mechanism of PD-1/PD-L1 and PD-1/PD-L2.Additionally,the method, which was based on the literature mining and bioinformatics,is good to put the biological literature to rational utilization and to pro-vide guidance for experiments.%目的：构建程序性死亡-1（PD-1）及其配体与其他蛋白质的相互作用网络，加深对 PD-1信号通路研究的认识，为 PD-1及其相关配体的基础及临床应用研究提供理论资料。方法通过 PubMed 检索 PD-1及其配体的研究文献，基于文献挖掘对已报道的与 PD-1及其配体存在相互作用的蛋白质进行统计，并以这部分蛋白质进行二次检索及文献挖掘统计，最后用软件 Cyto-scape 构建相互作用网络并进行分析；寻找网络中与细胞迁移有关的分子及其与 PD-L1之间的关系，并利用荧光定量 PCR 及迁移试验进行验证。结果在构建出的 PD-1／PD-L1及 PD-1／PD-L2分子互作网络中分别共计122个、126个分子，这些分子在 T 细胞受体信号通路、细胞黏附、JAK-STAT 信号通路及细胞因子间相互作用等众多生物过程中起到重要作用；基于互作网络显示， PD-L1会间接影响到 CXCR4的表达，这一推测被荧光定量 PCR 及迁移试验结果所支持。结论通过生物信息学手段对互作网络蕴含的信息进行挖掘发现，PD-1／PD-L1通路与 PD-1／PD-L2通路的作用机制存在差异。同时，利用基于文献挖掘及生物信息学的方法研究 PD-1信号通路是1种可以合理利用生物文献数据，为实际试验提供指导的好方法。