Comprehensive Analysis Of MicroRNA-messengerRNA Regulatory Network In Gemcitabine-resistant T24 Bladder Cancer Cells

Objective: Chemotherapy is still standard treatment for unresectable bladder cancer or distant metastases.The chemotherapy resistance always occurs after a period of treatment indicating unfavourable prognosis.The present study aimed to explore the molecular mechanism of chemoresistance in bladder cancer cells.Methods: The gene expression profiles of GSE77883,including three untreated T24 cells samples and three gemcitabine-resistant T24 cells samples,was downloaded from Gene Expression Omnibus database(GEO).The screening of differentially expressed genes(DEGs),gene function analysis and interaction prediction between micro RNA(mi RNA)and DEGs were performed by R software.Then the protein-protein interaction(PPI)was constructed and visualized by Cytoscape software as well as mi RNA-DEGs networks.Finally,small molecule drugs,with potential synergistic or antagonistic effects to GEM,were identified using the Connectivity Map(CMAP)database.Results: A total of536 up-regulated and 513 down-regulated genes were screened and mainly enriched in oxidative stress response and signaling pathways related to ECM-receptor interaction and focal adhesion.PPI network showed IL6,TNF and KIF11 were key genes and three modules were obtained.In addition,the mi RNA-DEGs regulatory networks included 18 mi RNAs and 185 DEGs,including mi R-182-5p,mi R-590-3p,mi R-320 a and mi R-1 and serum-and glucocorticoid-regulated kinase 1(SGK1).Finally,82 small molecules with antagonistic or synergistic effect to GEM were screened,including irinotecan,camptothecin,mitoxantrone,SC-560,NS-398 and scriptaid.Conclusion: we have investigated the molecular mechanisms driving GEM-resistence in bladder cancer cells that would contribute to the development of chemotherapy for advanced bladder cancer.