Identification Of Key Genes And Pathways At The Downstream Of YB-1 In Breast Cancer Cells By Bioinformatics Analysis

Objective:To identify the key downstream genes of YB-1 in breast cancer cells.Methods:Firstly,the dataset GSE95299 and GSE63562 were obtained from the Gene Expression Omnibus database.Secondly,by analyzing the two datasets,we respectively screened out the differentially expressed genes(DEGs)between YB-1 overexpression breast cancer cell group and untreated breast cancer cell group,and the DEGs between YB-1 shRNA breast cancer cell group and control breast cancer cell group;DEGs that were consistent with YB-1 expression were obtained by venn analysis.Then,functional and pathway enrichment analysis of differentially expressed genes were performed using DAVID database,FunRich and KOBAS bioinformatics tools.The protein-protein interaction(PPI)network was constructed by STRING and Cytoscape.The Kaplan-Meier plotter tool was used to evaluate DEGs that were associated with breast cancer prognosis.Finally,the NCBI database and Genomatix software were applied to perform promoter analysis of differentially expressed genes.Results:2354 up-regulated and 1740 down-regulated differentially expressed genes were screened out from YB-1 overexpressed breast cancer cell group and untreated breast cancer cell group;737 up-regulated and 849 down-regulated differentially expressed genes were identified from YB-1 shRNA breast cancer cell group and control breast cancer cell group;After venn analysis,a total of 185 genes with consistent expression trend were obtained,including 147 up-regulated differentially expressed genes that were positively correlated with YB-1 expression and 38 down-regulated differentially expressed genes that were negatively correlated with YB-1 expression.Functional enrichment analysis showed that differential genes were mainly enriched in apoptotic processes,drug response,cytoplasmic perinuclear regions and mitochondrial outer membranes;Pathway enrichment analysis revealed that differential genes were mainly enriched in NF-?B signaling pathway,Cell adhesion molecules,TNF signaling pathway,Platinum resistance,PI3K-Akt signaling pathway,Jak-STAT signaling pathway,Transcriptional deregulation in cancer.Through further analysis,17 genes that related to the overall survival of breast cancer patients were obtained,including YB-1,11 up-regulated DEGs and 5 down-regulated DEGs.Promoter analysis of these 16 genes revealed that CDKN1B,CD276,CTSV,CTSV,CXCL8,HTATIP2,RBPMS2,RHBPF2,RRBP1 and SLC2A6 promoter region contained YB-1 binding sites.Conclusions:CDKN1B,CD276,CTSV,CTSV,CXCL8,HTATIP2,RBPMS2,RHBPF2,RRBP1 and SLC2A6 may be the downstream key genes for YB-1 signaling pathway.And YB-1 may be involved in the signaling pathways of tumorgenesis and progression in breast cancer.