基于生物信息大数据及分子对接预测茵陈抗肝癌机制

Predicting of Yinchen′s (Oriental Wormwood) Anti-liver Cancer Mechanism Based on Bioinformatics Big Data and Molecular Docking

目的:基于生物大数据、网络药理学及分子对接虚拟预测的方法,探讨中药茵陈对于原发性肝癌的作用机制。方法:利用中药系统药理学数据库和分析平台(TCMSP)、DrugBank数据库对茵陈所含化学成分进行筛选并预测其作用靶点,通过GeneCards数据库、CTD数据库获得原发性肝癌的相关靶点。利用DrawVenDiagram平台制作韦恩图,获得两者的交集靶点蛋白,通过Cytoscape3.6构建出蛋白互作图。通过DAVID分析工具采集到的靶点蛋白从生物过程(biological process,BP)、分子功能(molecular function,MF)和细胞组分(cellular component,CC)三方面进行基因本体功能富集分析和KEGG通路分析。结果:从TCMSP、DrugBank数据库筛选出茵陈的13种化学成分,其中预测到166个靶点,通过CTD、GeneCards数据库预测到200个与原发性肝癌相关的靶点,韦恩图显示40个潜在靶标;PPI网络靶点蛋白有20条GO功能富集和4条主要的KEGG通路富集,并对相关靶点进行Docking验证。结论:茵陈大概通过RNA聚合酶II启动子转录的正调控、转录DNA模板、RNA聚合酶II启动子转录的负调控、转录的正调控等生物过程,并涉及转录因子活性、序列特异性DNA结合蛋白、DNA结合、染色质结合等分子功能发挥治疗原发性肝癌的作用。其作用机制可能与癌症蛋白聚糖信号通路、HTLV-I信号通路、MAPK信号通路、TNF信号通路等有关。

Objective:This study is based on biological big data,network pharmacology and molecular docking virtual prediction methods to explore the mechanism of the Chinese medicine Yinchen(Oriental wormwood)on primary liver cancer.Methods:First,use the Chinese Medicine System Pharmacology Database and Analysis Platform(TCMSP)and DrugBank database to screen the chemical components contained in Yinchen(Oriental wormwood)and predict their targets,and obtain the relevant targets of primary liver cancer through the GeneCards database and CTD database;Then,use the DrawVenDiagram platform to make a Venn diagram,obtain the intersection target protein of the two,and construct a protein interaction map through Cytoscape 3.6;finally,the target protein collected by the DAVID analysis tool is collected from the biological process(biological process,BP),molecular function(molecular function,MF)and cellular component(cellular component,CC)three aspects of gene ontology function enrichment analysis and KEGG pathway analysis.Results:13 chemical components of Yinchen(Oriental wormwood)were screened from TCMSP and DrugBank databases,of which 166 targets were predicted,and 200 targets related to primary liver cancer were predicted by CTD and GeneCards databases.The Venn diagram showed 40 Two potential targets;PPI network target protein has 20 GO functional enrichment and 4 main KEGG pathway enrichment,and Docking verification of related targets.Conclusion:It is probably through biological processes such as positive regulation of RNA polymerase II promoter transcription,transcription DNA template,negative regulation of RNA polymerase II promoter transcription,and positive regulation of transcription,and involve transcription factor activity and sequence-specific DNA Molecular functions such as binding protein,DNA binding,and chromatin binding play a role in the treatment of primary liver cancer.Its mechanism of action may be related to the cancer proteoglycan signaling pathway,HTLV-I signaling pathway,MAPK signaling pathway,TNF signaling pathway and other signaling pathways.