首页|基于网络药理学和生物信息学探索金雀异黄酮对肝细胞癌的作用机制

基于网络药理学和生物信息学探索金雀异黄酮对肝细胞癌的作用机制

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目的 通过网络药理学及生物信息学方法阐明金雀异黄酮对肝细胞癌的作用机制。方法 利用网络药理学、生物信息学和实验验证方法。从Pharm Mapper数据库获取金雀异黄酮的潜在作用靶点。使用Gene Cards数据库获取肝细胞癌的致病基因,分析确定金雀异黄酮潜在靶点与肝细胞癌相关靶点的交集基因。采用TCGA的肝细胞癌组织样本和正常组织样本的RNA测序数据及临床信息,筛选出差异表达的共同靶基因,并进行基因本体(GO)功能注释和京都基因与基因组百科全书(KEGG)通路富集分析。通过单因素Cox分析筛选影响患者总体生存期的差异表达基因(DEGs),利用STRING平台构建DEGs的靶点交互网络,并筛选核心基因进行验证。进行分子对接试验,检测金雀异黄酮对肝细胞癌增殖的影响。结果 共筛选出235个金雀异黄酮的潜在作用靶点和9 415个肝细胞癌的治疗靶点,其中40个差异表达的共同靶基因影响患者的预后。其中,ESR1、AR、HRAS、CCNA2、MMP9和CYP3A4为核心靶点。GO功能注释富集分析获得333个富集项,KEGG通路富集分析获得23个富集结果。分子对接结果显示,金雀异黄酮与核心靶蛋白有强烈的结合能力。体外实验证实,金雀异黄酮显著抑制了肝细胞癌的增殖。结论 金雀异黄酮通过多个代谢和信号通路抑制肝细胞癌的发展机制。ESR1、AR、HRAS、CCNA2、MMP9和CYP3A4的表达水平可用于预测肝细胞癌患者的预后,为治疗提供有价值的靶点。
The mechanism of genistein on hepatocellular carcinoma based on network pharmacology and bioinformatics
Objective To elucidate the mechanism of genistein on hepatocellular carcinoma by network pharmacology and bioinformatics.Methods Network pharmacology,bioinformatics and experimental valida-tion were used.The potential targets of genistein were obtained from the Pharm Mapper database.Gene Cards database was used to obtain the pathogenic genes of hepatocellular carcinoma,and the intersection genes of po-tential targets of genistein and hepatocellular carcinoma-related targets were analyzed and determined.The clinical information of TCGA hepatocellular carcinoma tissue samples and normal tissue samples were used to screen out differentially expressed common target genes,and gene ontology(GO)functional annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed.The dif-ferential genes(DEGs)affecting the overall survival of patients were screened by univariate Cox analysis.The STRING platform was used to construct the target interaction network of DEGs,and the core genes were screened for verification.Molecular docking experiments were performed to detect the effect of genistein on the proliferation of hepatocellular carcinoma.Results A total of 235 potential targets of genistein and 9 415 therapeutic targets of hepatocellular carcinoma were screened out,of which 40 differentially expressed com-mon target genes affected the patient's back.Among them,ESR1,AR,HRAS,CCNA2,MMP9 and CYP3A4 were the core targets.GO functional annotation enrichment analysis obtained 333 enrichment items,and KEGG pathway enrichment analysis obtained 23 enrichment.The results of molecular docking showed that genistein had a strong binding ability with the core target protein.In vitro experiments confirmed that genistein significantly inhibited the proliferation of hepatocellular carcinoma.Conclusion Genistein inhibits the development of hepatocellular carcinoma through multiple metabolic and signaling pathways.The expres-sion levels of ESR1,AR,HRAS,CCNA2,MMP9 and CYP3A4 can be used to predict the prognosis of patients with hepatocellular carcinoma and provide valuable targets for treatment.

Liver tumorNetwork pharmacologyBioinformaticsGenisteinHepatocellular carcinoma

林丽桥、黄敬媚、黄小晓、李政钊

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广西医科大学第二临床医学院,广西 南宁 530021

广西医科大学第二附属医院急诊科,广西 南宁 530007

肝肿瘤 网络药理学 生物信息学 金雀异黄酮 肝细胞癌

广西自然科学基金青年基金

2022GXNSFAA035459

2024

现代医药卫生
重庆市卫生信息中心

现代医药卫生

影响因子:0.758
ISSN:1009-5519
年,卷(期):2024.40(11)