Analysis of PPI networks of transcriptomic expression identifies hub genes associated with Newcastle disease virus persistent infection in bladder cancer

Abstract

AbstractMotivationBladder cancer cells acquire persistent infection associated with oncolytic Newcastle disease virus (NDV) in which its molecular events are still unclear. This poses a potential problem for oncolytic virus application for cancer therapy. To unravel the molecular mechanism underlying the development of NDV persistent infection in bladder cancer, we used mRNA expression profile of the persistently infected bladder cancer cells to construct PPI network.ResultsBased on path and module exploring in the PPI network, the bridges were found mainly from pathways of p53 signalling, ECM-receptor interaction, and TGF-beta signalling by the upregulated mRNAs, to the antigen processing and presentation, protein processing in endoplasmic reticulum, completement and coagulation cascades by the downregulated mRNAs in NDV persistent TCCSUPPi cells. In persistent EJ28Pi cells comparatively, connections were identified mainly from pathways of renal carcinoma, viral carcinogenesis, Ras signalling and cell cycle by the upregulated mRNAs, to the Wnt signalling, HTLV-I infection and pathways in cancer by the downregulated mRNAs. This connection was mainly dependent on of RPL8- HSPA1A/HSPA4 in TCCSUPPi cells and EP300, PTPN11, RAC1 - TP53, SP1, CCND1 and XPO1 in EJ28Pi cells. Oncomine validation showed that the top hub genes identified in the network that includes RPL8, THBS1, F2 from TCCSUPPi and TP53 and RAC1 from EJ28Pi are involved in the development and progression of bladder cancer. Protein-drug interaction network, have identified several drugs targets that could be used to disconnect the linkages between modules and prevent bladder cancer cells from acquiring NDV persistent infection. This is the first time reporting the PPI network analysis of differentially expressed mRNAs of the NDV persistently infected bladder cancer cell lines which provide an insight into screening drugs that could be used together with NDV to manage bladder cancer resistance to therapy and progression.