Analysis of the association between Salidroside and ferroptosis in gastric cancer based on omics approaches
Objective:To investigate the Salidroside-regulated ferroptosis mechanism in gastric cancer using molecular docking,network pharmacology,and clinical data bioinformatics.Methods:The drug targets for Salidroside were sourced from the Symmap and UniProt databases;the genes related to ferroptosis were sourced from the ferrDb database;the disease targets for gastric cancer were sourced from the GeneCards,OMIM,and TTD databases,Cytoscape 3.9.1 software was utilized to con-struct the component-target network,and Cytoscape and the STRING database were utilized to construct the protein-protein interaction(PPI)network.Using the Kaplan-Meier plotter to examine the correlation between core gene expression and patient survival,and the database UALCAN to assess the transcript levels of the core gene for Salidroside-targeted ferroptosis.Gene ontology(GO)function and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis were performed using the DAVID database.RCSB and AutoDock Vina 1.1.2 software were used to complete the molecular docking of Salidroside with the core genes and to validate their binding activities with the target genes.Results:There were 60 genes that were Salidroside-targeted,including 20 ferroptosis genes.DDIT3,GSK3B,HIF1A,MAPK1,MTOR(FRAP),PARP1,PIK3CA,RELA(NFKB3),SIRT1,VEGFA,PRKAA1,MAPK3,and PRKAA2 gene mRNA expressions were aberrantly expressed in gas-tric cancer(P＜0.05).The aberrant expression ofDDIT3,MAPK3,VEGFA,PRKAA2,RELA(NFKB3),HIF1A,MAPK1,PIK3CA,SIRT1,PRKAA1,PARP1 mRNA were correlated with the prognosis of gastric cancer patients(P＜0.05).GO analysis was mainly enriched in the regulation of cell division,proliferation and apoptosis,while KEGG analysis was mainly enriched in the regu-lation of PI3K-Akt,HIF-1,FoxO signaling pathways,apoptosis,autophagy,Kaposi's sarcoma-associated herpesvirus infec-tion,reactive oxygen species chemical carcino genesis,cancer pathway,PD-L1 expression in tumors and PD-1 checkpoint pathway and longevity regulation pathway.According to the molecular docking data,Salidroside exhibited improved binding activity with PRKAA2,SIRT1,VEGFA,and DDIT3(-6.0＜score＜-4.0)and high binding activity with PARP1,PRKAA1,HIF1A,MAPK1,RELA(NFKB3),MAPK3,and PIK3G4(score＜-6.0).Conclusion:Salidroside regulates the ferroptosis mechanism in gastric cancer with multi-target and multi-pathway synergistic effects,mainly acting on DDIT3,MAPK3,VEGFA,PRKAA2,RELA(NFKB3),HIF1A,MAPK1,PIK3CA,SIRT1,PRKAA1,PARP1 targets,and regulating the PI3K-Akt,HIF-1,and FoxO signaling pathways and so on.
万方数据
维普
