摘要
目的:从网络药理学角度探讨人参皂苷Rg1与神经母细胞瘤(NB)的核心靶点及其分子作用机制。方法:利用PharmMapper等数据库筛选Rg1治疗NB的作用靶点并进行GO/KEGG富集分析、核心靶点筛选、Hub基因预后模型以及分子对接模型,分析Hub基因在神经母细胞瘤作用机制。结果:初步筛选出Rg1-NB交集靶点129个,GO、KEGG分析结果发现Rg1可能通过PI3K/Akt、MAPK、JAK/STAT信号通路影响神经母细胞瘤增殖、迁移、凋亡等生物过程;PPI互作聚类分析结果表明,Rg1可能通过调控细胞凋亡、生物节律、酪氨酸蛋白激酶等发挥治疗作用;通过对Rg1治疗NB作用靶点进行Hub基因筛选以及基因、表型分析,发现Rg1治疗Hub基因为AKT1、MTOR、STAT3,进一步预后模型分析发现STA3高表达组的NB患者的生存率显著高于低表达,说明STAT3为预后保护因素,且Rg1与STAT3有9个结合位点,结合自由能为-6.57 kcal/mol,结合效果较好。结论:通过数据库筛选出3个人参皂苷Rg1治疗神经母细胞瘤核心靶点依次为AKT1、MTOR、STAT3,进一步通过建立核心基因预后模型、分子对接实验及GO、KEGG分析表明,人参皂苷Rg1可能通过JAK/STAT信号通路发挥功能,影响神经母瘤细胞的发展,为Rg1治疗神经母细胞瘤分子机制、药物靶点的选择及新型治疗技术的开发提供一定的参考和理论依据。
Objective:To explore the core targets and molecular mechanisms of ginsenoside Rg1 and neuroblastoma from the perspective of network pharmacology.Methods:Using PharmMapper and other databases to screen the targets of Rg1 in the treatment of NB,GO/KEGG enrichment analysis,core target screening,Hub gene prognostic model and molecular docking model were used to analyze the mechanism of Hub gene in neuroblastoma.Results:129 Rg1-NB intersection targets were preliminarily screened out,and GO and KEGG analysis showed that Rg1 may affect neuroblastoma proliferation,migration,apoptosis and other biological processes through PI3K/AKT,MAPK,JAK/STAT signaling pathways.The results of PPI interaction cluster analysis showed that Rg1 may play a therapeutic role by regulating apoptosis,biological rhythm,tyrosine protein kinase,etc;Through Hub gene screening and gene-phenotype analysis of Rg1 treatment targets for NB,it was found that the Rg1 treatment Hub genes were AKT1,MTOR,and STAT3.Further prognostic model analysis found that the survival rate of NB patients in the STA3 high expression group was significantly higher than that of low expression,indicating that STAT3 is a prognostic protective factor,and Rg1 and STAT3 have 9 binding sites,and the binding free energy is-6.57kcal/mol,and the binding effect is better.Conclusion:In summary,in this study,we screened out the three core targets of ginsenoside Rg1 in the treatment of neuroblastoma through the database,which are AKT1,MTOR,and STAT3.Further,through the establishment of core gene prognostic models,molecular docking experiments,and GO and KEGG analysis,it was shown that ginsenoside Rg1 may function through the JAK-STAT signaling pathway and affect the development of neuroblastoma cells.References and theoretical basis.
作者
孙天霞
秦华聪
卢佳宏
段启栋
赵雨
刘志美
杨晶晶
慧芳
惠歌
Sun Tianxia;Qin Huacong;Lu Jiahong;Duan Qidong;Zhao Yu;Liu Zhimei;Yang Jingjing;Hui Fang;Hui Ge(Jilin Ginseng Academy,Changchun University of Chinese Medicine,Changchun 130117,China;The Hospital Affiliated to Changchun University of Chinese Medicine,Changchun 130117,China;Tonghua College of Life Science,Tonghua Normal University,Tonghua 134000,China;School of Pharmacy,Changchun University of Chinese Medicine,Changchun 130117,China)
出处
《亚太传统医药》
2024年第5期169-174,共6页
Asia-Pacific Traditional Medicine
基金
吉林省自然科学基金面上项目(医学科学领域)(YDZJ202301ZYTS204)。
