黄精通过调控拓扑异构酶Ⅱ-α抗胃癌的分子机制研究  

Molecular Mechanism of the Anti-gastric Cancer Effect of Polygonatum sibiricum by Regulating TopoisomeraseⅡAlpha

作　　者：余静 刘启伟 阚红星 杨银凤 YU Jing;LIU Qiwei;KAN Hongxing;YANG Yinfeng(School of Medical Information Engineering,Anhui University of Chinese Medicine,Anhui Hefei 230012,China)

机构地区：[1]安徽中医药大学医药信息工程学院,安徽合肥230012

出　　处：《安徽中医药大学学报》2024年第5期72-78,共7页Journal of Anhui University of Chinese Medicine

基　　金：安徽省教育厅高校中青年教师培养行动项目(JNFX2023020);安徽省教育厅杰青项目(2022AH020042);安徽省高等学校科学研究重大项目(2023AH040102)。

摘　　要：目的揭示黄精调控DNA拓扑异构酶Ⅱ-α(topoisomeraseⅡalpha,TOP2A)抗胃癌的分子机制。方法首先借助“limma”R包对来源于癌症基因组中胃癌与正常组织的转录组数据进行差异表达基因筛选;然后采用加权基因共表达网络分析、CytoHubba的度值和邻域组件中心性算法筛选Hub基因,并基于Hub基因对黄精中抗胃癌成分进行虚拟筛选;最后应用动力学模拟对筛选出来的关键化合物和靶基因相互作用关系进行验证,并揭示其抗胃癌的分子机制。结果共鉴定出382个差异表达基因和6个Hub基因,即TOP2A、CDK1、AURKB、BUB1、CCNA2和MCM4;虚拟筛选发现黄精活性成分薯蓣皂苷元与TOP2A结合能力较好;分子动力学模拟证实,薯蓣皂苷元可稳定结合并抑制TOP2A的表达,验证了虚拟筛选结果的准确性;生物学功能富集发现TOP2A主要干预细胞周期通路、p53信号通路和FoxO信号通路。结论黄精主要通过薯蓣皂苷元调控TOP2A并作用于细胞周期通路、p53信号通路和FoxO信号通路而达到抗胃癌的作用。Objective To investigate the molecular mechanism of the anti-gastric cancer effect of Polygonatum sibiricum by regulating DNA topoisomeraseⅡalpha(TOP2A).Methods The"limma"R package was used to analyze the transcriptome data of gastric cancer tissue and normal tissue in TCGA and identify differentially expressed genes(DEGs);weighted gene co-expression network analysis and CytoHubba’s Degree and MNC algorithms were used to obtain Hub genes,and virtual screening was performed to identify the anti-gastric cancer components in Polygonatum sibiricum based on the Hub genes;molecular dynamics simulation was used to verify the interaction between the key compounds and the target genes and reveal their molecular mechanism of action against gastric cancer.Results A total of 382 DEGs and 6 Hub genes were identified,namely TOP2A,CDK1,AURKB,BUB1,CCNA2,and MCM4.Virtual screening showed that dioscin,an active component of Polygonatum sibiricum,had a better binding ability to TOP2A.Molecular dynamics simulation confirmed that dioscin could stably bind to TOP2A and inhibit its expression,which verified the accuracy of virtual screening.Biological function enrichment showed that TOP2A mainly interfered with the cell cycle pathway,the p53 signaling pathway,and the FoxO signaling pathway.Conclusion Polygonatum sibiricum exerts an anti-gastric cancer effect by regulating TOP2A through dioscin and acting on the cell cycle pathway,the p53 signaling pathway,and the FoxO signaling pathway.

关 键 词：黄精 胃癌 虚拟筛选 分子动力学 分子机制 

分 类 号：R735.2[医药卫生—肿瘤]