生物信息学和网络药理学分析山奈酚通过靶向CDK1和TOP2A抑制胶质瘤增殖
Kaempferol Inhibiting Glioma Proliferation by Targeting CDK1 and TOP2A Based on Bioinformatics and Network Pharmacology Analysis
摘要: 目的：本研究旨在通过生物信息学和中药网络药理学分析探索影响胶质瘤恶性进展的中药靶点及有效成分。方法：通过基因表达数据库中GSE29796、GSE50161和GSE66354数据集分析胶质瘤与癌旁组织的差异表达基因。通过GO和KEGG富集分析，利用Cytoscape获得hub基因。从中药系统药理学数据库和分析平台中获得白芍、人参、石菖蒲和知母等四种中药有效成分和相关靶点，利用Cytoscape软件将目标差异表达基因构建蛋白质–蛋白质相互作用网络。通过对比关键成分所对应的潜在靶点基因和hub基因，获得潜在治疗靶点基因。结果：差异表达基因的GO富集分析提示参与细胞粘附、细胞分裂、有丝分裂核分裂和G2/M有丝分裂细胞周期等过程，KEGG结果提示参与4个信号通路，包括p53信号通路、细胞周期、粘着斑和癌症中的蛋白多糖。生物信息学和网络药理学分析共筛选到11个潜在靶点基因和8种关键成分构建化合物–靶标网络，PPI网络和拓扑分析获取潜在治疗靶点基因：CDK1和TOP2A。结论：山奈酚可能通过靶向CDK1和TOP2A抑制胶质瘤增殖，为胶质瘤治疗提供了一种新的途径。
Abstract: Background: The purpose of this study was to explore the targets and active components of traditional Chinese medicine (TCM) affecting the malignant progression of glioma through bioinformatics and TCM network pharmacology analysis. Methods: Differentially expressed genes in glioma and adjacent tissues were analyzed by GSE29796, GSE50161 and GSE66354 datasets in gene expression database. Through GO and KEGG enrichment analysis, the hub gene was obtained by Cytoscape. Four active components and related targets of Paeonia lactiflora, Ginseng, Acorus graminis and Anemarrhenae anemarrhenae were obtained from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, and the protein-protein interaction network was constructed by using Cytoscape software. Potential target genes and HUB genes corresponding to key components were compared to obtain potential therapeutic target genes. Results: GO enrichment analysis of differentially expressed genes suggests that they are involved in protein binding, cell adhesion, cell division, mitotic nuclear division and G2/M transition of mitotic cell cycle etc. KEGG results suggested that four signaling pathways were involved, including p53 signaling pathway, cell cycle, focal adhesion and proteoglycans in cancer. A total of 11 potential target genes and 8 key components were screened by bioinformatics and network pharmacology analysis to construct a compound-target network. PPI network and topological analysis were used to obtain potential therapeutic target genes: CDK1 and TOP2A. Conclusion: Kaempferol may inhibit the proliferation of gliomas by targeting CDK1 and TOP2A, providing a new approach for the treatment of gliomas.
文章引用：李怀旭, 高鹏, 杨亚飞, 代兴亮, 叶雷, 程宏伟. 生物信息学和网络药理学分析山奈酚通过靶向CDK1和TOP2A抑制胶质瘤增殖[J]. 临床医学进展, 2022, 12(1): 519-529. https://doi.org/10.12677/ACM.2022.121077

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