Huang Jun-Ting, Chen Jian-Ning, Bi Yuan-Hua, Gong Li-Ping, Zhang Jing-Yue, DU Yu, Shao Chun-Kui
Department of Pathology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.
Department of Emergency, The First Affiliated Hospital, Guangzhou Medical University, Guangzhou, People's Republic of China.
Onco Targets Ther. 2021 Oct 23;14:5169-5182. doi: 10.2147/OTT.S332513. eCollection 2021.
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.
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.
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.
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.
广泛认为爱泼斯坦-巴尔病毒（EBV）可引发多种肿瘤，而EBV相关胃癌（EBVaGC）是胃癌的一种特殊类型。它与EBV阴性胃癌具有明显不同的临床特征和病理表现，但其进展情况仍不清楚。通过全基因组转录组分析检测到的病毒感染引发的潜在癌症进展已在众多疾病中得到证实。
我们进行了比较RNA测序，以确定胃癌和EBVaGC细胞系之间的基因表达特征。使用基因本体论和通路富集分析差异表达（DE）基因。
EBV感染后，在胃癌细胞中检测到总共4438个DE mRNA、3650个DE长链非编码RNA（lncRNA）和248个DE环状RNA（circRNA），其中大多数与肿瘤发生高度相关。同样，EBV编码RNA和非编码RNA在EBVaGC中也得到了很好的补充。根据生物信息学分析，DE mRNA可能有助于EBV感染宿主细胞的完成并调节有丝分裂。与肌动蛋白结合并参与黏附连接以促进病毒与细胞之间的接触是DE lncRNA的潜在功能。DE circRNA的作用富集在DNA修复和蛋白质修饰方面，其中一个典型例子是作为miRNA海绵发挥作用。circRNA-miRNA-mRNA网络的建立有助于确定EBVaGC进展中的关键因素。
本研究首次系统地揭示了EBVaGC的转录组图谱，这将为未来的基因组、遗传学和分子机制研究提供重要资源。
