Molecular Mechanism of the Anti-gastric Cancer Effect of Polygonatum sibiricum by Regulating Topoisomerase Ⅱ Alpha
Objective To investigate the molecular mechanism of the anti-gastric cancer effect of Polygonatum sibiricum by reg-ulating DNA topoisomerase Ⅱ alpha (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-ex-pression 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 dy-namics 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.
万方数据
维普
