Abstract
BackgroundNewcastle disease virus (NDV) is an oncolytic virus with excellent selectivity against cancer cells, both in vitro and in vivo. Unfortunately, prolonged in vitro NDV infection results in the development of persistent infection in the cancer cells which are then able to resist NDV-mediated oncolysis. However, the mechanism of persistency of infection remains poorly understood.MethodsIn this study, we established persistently NDV-infected EJ28 bladder cancer cells, designated as EJ28P. Global transcriptomic analysis was subsequently carried out by microarray analysis. Differentially expressed genes (DEGs) between EJ28 and EJ28P cells identified by the edgeR program were further analysed by Gene Set Enrichment Analysis (GSEA) and Ingenuity Pathway Analysis (IPA) analyses. In addition, the microarray data were validated by RT-qPCR.ResultsPersistently NDV-infected EJ28 bladder cancer cells were successfully established and confirmed by flow cytometry. Microarray analysis identified a total of 368 genes as differentially expressed in EJ28P cells when compared to the non-infected EJ28 cells. GSEA revealed that the Wnt/β-catenin and KRAS signalling pathways were upregulated while the TGF-β signalling pathway was downregulated. Findings from this study suggest that the upregulation of genes that are associated with cell growth, pro-survival, and anti-apoptosis may explain the survivability of EJ28P cells and the development of persistent infection of NDV.ConclusionsThis study provides insights into the transcriptomic changes that occur and the specific signalling pathways that are potentially involved in the development and maintenance of NDV persistency of infection in bladder cancer cells. These findings warrant further investigation and is crucial towards the development of effective NDV oncolytic therapy against cancer.
Highlights
Newcastle disease virus (NDV) is an oncolytic virus with excellent selectivity against cancer cells, both in vitro and in vivo
We aimed to identify genes that are associated with persistent infection of NDV in EJ28 bladder cancer cells
Establishment of NDV-persistently infected EJ28 (EJ28P) cells When the EJ28 bladder cancer cells were first infected with the NDV strain AF2240 (MOI of 1), majority of the infected cells died
Summary
Newcastle disease virus (NDV) is an oncolytic virus with excellent selectivity against cancer cells, both in vitro and in vivo. NDV has been studied extensively in vitro and in vivo for its oncolytic properties against various types of cancers [2,3,4,5]. It was postulated that the selectivity of NDV is due to defects in antiviral responses that favour viral replication such as the production of interferons by cancer cells [7, 8]. While NDV mediates oncolysis through the activation of intrinsic and extrinsic apoptosis pathways [9], it can trigger a long-term adaptive immune response against infected cancer cells [10]
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