基于生物信息学分析Scoparone对肝癌的作用机制  

Analysis on the Mechanism of Action of Scoparone in Liver Cancer Based on Bioinformatics

作　　者：杨玉雯 姚元谦 吕建林[2] 刘英[1] YANG Yuwen;YAO Yuanqian;LYU Jianlin;LIU Ying(Guangxi University of Traditional Chinese Medicine,Nanning Guangxi 530001,China;The First Affiliated Hospital of Guangxi University of Traditional Chinese Medicine,Nanning Guangxi 530023,China)

机构地区：[1]广西中医药大学,广西南宁530001 [2]广西中医药大学第一附属医院,广西南宁530023

出　　处：《中医药导报》2023年第2期127-132,共6页Guiding Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金项目(81860839);广西自然科学基金项目(2020GXNSFAA238020);广西自然科学基金项目(2022GX NSFAA035446)。

摘　　要：目的:研究茵陈活性成分6,7-二甲氧基香豆素(Scoparone)治疗肝癌的分子机制。方法:使用GEO数据库下载肝癌的芯片数据,从TCMSP数据库检索Scoparone的作用靶点,使用R软件获取肝癌差异基因;通过Jvenn和Cytoscape3.9.1软件筛选两者交集靶点,构建蛋白互作网络,进一步使用R软件对核心交集靶点进行GO、KEGG分析;使用AutoDockTools1.5.7及AutoDockVina软件进行分子对接,对活性成分与核心靶点的结合能力进行验证;使用TCGA数据库进行核心基因的生存预后分析。结果:得到肝癌显著性差异基因1788个、Scoparaone作用靶点100个,筛选出药物-疾病交集靶点97个。PPI拓扑分析得出的核心靶点有JAK1、JAK2、EGFR、ICAM1、KDR等。GO功能富集分析主要涉及氧化应激反应、蛋白质酪氨酸磷酸化及修饰、PI3K级联的正调节等,KEGG通路分析在主要富集在EGFR酪氨酸激酶抑制剂耐药机制、PI3K/Akt信号通路、上皮细胞信号传导通路、Rap1信号通路、Ras信号通路、MAPK信号通路、VEGF信号通路等途径。分子对接验证显示,Scoparone与核心靶点间结合能<-5.0 kcal/mol。结论:Scoparone能通过调控JAK1、JAK2、EGFR、ICAM1、KDR等核心靶点,调控PI3K/Akt信号通路、上皮细胞信号传导通路、Rap1信号通路、Ras信号通路、MAPK信号通路、VEGF信号通路等途径,从而抑制肝癌细胞的增殖、侵袭,作用机制涉及氧化应激反应过程、蛋白质酪氨酸磷酸化及修饰、ATP结合等生物功能。Objective:To study the molecular mechanism of 6,7-dimethoxycoumarin(Scoparaone),the active ingredient of Inoceramus,in the treatment of liver cancer.Methods:Microarray technology for hepatocellular carcinoma was downloaded with the GEO database.The action targets of Scoparone was retrieved from the TCMSP database.The hepatocellular carcinoma differential genes were obtained by R software.The intersection targets of both were screened by Jvenn and Cytoscape 3.9.1 software to construct protein interaction networks.GO and KEGG analysis were further performed on the core intersection targets by R software.AutoDockTools 1.5.7 and AutoDockVina software were used to perform molecular docking and the binding ability of the active ingredient,in order to verify the core targets.The survival and prognosis of core genes were analyzed with TCGA database.Results:Totally 1788 genes with significant differences in liver cancer,and 100 Scoparaone action targets were obtained.A total of 97 drug-disease intersection targets were screened.The core targets derived from PPI topology analysis include JAK1,JAK2,EGFR,ICAM1,KDR,etc.GO functional enrichment analysis mainly involved oxidative stress response,protein tyrosine phosphorylation and modification,positive regulation of PI3K cascade,etc.The KEGG pathway analysis was mainly enriched in EGFR tyrosine kinase inhibitor resistance mechanism,PI3K/Akt signaling pathway,epithelial cell signaling pathway,Rap1 signaling pathway,Ras signaling pathway,MAPK signaling pathway,VEGF signaling pathway and other pathways.Molecular docking validation showed that the binding energy between each active ingredients of Inoceramus and the core targets was<-5.0 kcal/mol.Conclusion:Scoparone can regulate PI3K/Akt signaling pathway,epithelial cell signaling pathway,Rap1 signaling pathway,Ras signaling pathway,MAPK signaling pathway and VEGF signaling pathway through the regulation of JAK1,JAK2,EGFR,ICAM1,KDR and other core targets,to inhibit the proliferation and invasion of liver cancer cells.The mechanism

关 键 词：肝癌 6 7-二甲氧基香豆素 茵陈 GEO芯片挖掘 TCGA数据库 分子对接 

分 类 号：R285.5[医药卫生—中药学]