%0 Journal Article
%T 基于WGCNA和网络药理学探讨小檗碱治疗结直肠癌的作用机制<br>WGCNA and Network Pharmacology Reveal Targets and Mechanisms of Action of Berberine in Colorectal Cancer Treatment
%A 钟林恬
%A 李红燕
%A 刘世茹
%J Advances in Clinical Medicine
%P 818-827
%@ 2161-8720
%D 2024
%I Hans Publishing
%R 10.12677/ACM.2024.143776
%X 目的：探讨小檗碱治疗结直肠癌的潜在治疗靶点和分子机制。方法：使用Swiss Target Prediction、Comparative Toxicogenomics、Target Net和Binding数据库筛选出小檗碱的活性成分及基因靶点。同时，基于GEO数据库的GSE90627数据集进行WGCNA分析，以识别结直肠癌的相关靶点。通过绘制维恩图以获得疾病–药物基因集。利用STRING数据库构建了蛋白互作网络(PPI)。利用Cytoscape软件进行拓扑分析，得到关键聚类。对关键簇基因进行了功能富集分析。最后，通过在线分子对接网站进行虚拟验证。结果：经过一系列的生物信息学分析，获得了包含35个基因的关键簇。富集分析结果表明，关键簇基因主要富集在p53和FOXO信号通路中。使用PPI和WGCNA分析鉴定出4个最重要的生物学靶标：WD重复蛋白74 (WDR 74)、细胞周期蛋白依赖性激酶4 (CDK 4)、极光激酶A (AURKA)和细胞周期蛋白1 (CCNE 1)。分子对接结果表明，上述4个靶标均能与小檗碱稳定结合。结论：本研究利用生物信息学和网络药理学方法筛选和鉴定了小檗碱治疗结直肠癌的生物学靶点和分子机制，为结直肠癌的诊断和治疗提供了新的建议和理论支持。<br />
Objective: To explore the potential therapeutic target and molecular mechanism of berberine in the treatment of colorectal cancer. Methods: Swiss Target Prediction, Comparative Toxicogenomics, TargetNet and Binding databases were used to screen the active components and gene targets of berberine. In parallel, WGCNA analysis was performed based on the GSE90627 dataset from the GEO database to identify relevant targets for colorectal cancer. The disease-drug gene set is ob-tained by drawing a Venn diagram. A protein interaction network (PPI) was constructed using STRING database. Topology analysis was performed using Cytoscape software to obtain key cluster. The key cluster genes were analyzed for functional enrichment. Finally, virtual validation was per-formed through an online molecular docking website. Results: After a series of bioinformatics anal-yses, key clusters containing 35 genes were obtained. Enrichment analysis showed that key cluster genes were mainly enriched in p53 and FOXO signal pathways. Four of the most important biologi-cal targets were identified: WD repeat protein 74 (WDR74), cyclin dependent kinase 4 (CDK4), au-rora kinase A (AURKA), and cyclin E1 (CCNE 1). Molecular docking results showed that all four tar-gets could bind to berberine stably. Conclusion: In this study, biological targets and molecular mechanisms of berberine in the treatment of colorectal cancer were screened and identified by bi-oinformatics and network pharmacology methods, which provided new suggestions and theoretical support for the diagnosis and treatment of colorectal cancer.
%K 小檗碱，结直肠癌，网络药理学，分子对接<br>Berberine
%K Colorectal Cancer
%K Network Pharmacology
%K Molecular Docking
%U http://www.hanspub.org/journal/PaperInformation.aspx?PaperID=82863