Comparative Transcriptome Provides a Systematic Perspective on Epstein–Barr Virus-Associated Gastric Carcinoma Cell Lines

Jun-Ting Huang,1,2 Jian-Ning Chen,1 Yuan-Hua Bi,1 Li-Ping Gong,1 Jing-Yue Zhang,1 Yu DU,1 Chun-Kui Shao1 1Department of Pathology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 2Department of Emergency, The First Affiliated Hospital, Guangzhou Medical University, Guangzhou, People’s Republic of ChinaCorrespondence: Chun-Kui ShaoDepartment of Pathology, The Third Affiliated Hospital, Sun Yat-sen University, No. 500 Tian He Road, Guangzhou, 510000, People’s Republic of ChinaEmail shaochk@mail.sysu.edu.cnPurpose: Epstein–Barr virus (EBV) is widely recognised to cause various tumours, and EBV-associated gastric carcinoma (EBVaGC) is a special type of GC. It has obviously different clinical features and pathological manifestations from EBV-negative gastric carcinoma, but its progression remains elusive. The underlying cancer progression of viral infection detected by genome-wide transcriptome analysis has been demonstrated in numerous diseases.Methods: We performed comparative RNA sequencing to identify gene expression signatures between GC and EBVaGC cell lines. The differentially expressed (DE) genes were analysed using gene ontology and pathway enrichment.Results: A total of 4438 DE mRNAs, 3650 DE long non-coding RNAs (lncRNAs), and 248 DE circular RNAs (circRNAs) were detected in GC cells after EBV infection, most of which were highly related to oncogenesis. Likewise, EBV-coding RNA and non-coding RNA were also well-supplemented in EBVaGC. According to bioinformatics, DE mRNAs may contribute to the completion of EBV-infected host cells and modulate mitosis. Binding to actin and participating in adherens junctions to promote contact between the virus and cells are a potential function of DE lncRNAs. The roles of DE circRNAs were enriched in DNA repair and protein modification, and a typical example of this is acting as an miRNA sponge. The establishment of a circRNA-miRNA-mRNA network helps to determine the key elements in the progression of EBVaGC.Conclusion: This study is the first to systematically reveal the transcriptome landscape of EBVaGC, which will provide an essential resource for genomic, genetic, and molecular mechanisms in the future.Keywords: transcriptome, RNA-sequencing, bioinformatics, regulatory network, EBV-associated gastric cancer