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Comprehensive profiling of EBV gene expression in nasopharyn- geal carcinoma through paired-end transcriptome sequencing

引用

Frontiers of Medicine 2016年第1期10卷 61-75页

作者： Lijuan Hu Zhirui Lin yanhengwu Juqin Dong Bo Zhao Yanbing Cheng Peiyu Huang Lihua Xu Tianliang Xia Dan Xiong Hongbo Wang Manzhi Li Ling Guo Elliott Kieff YixinZeng State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine and Department of Experimental Research Sun Yat-sen University Cancer Center Guangzhou 510060 China First Affiliated Hospital of Jinan University Guangzhou 510630 China Department of Nasopharyngeal Carcinoma Sun Yat-sen University Cancer Center Guangzhou 510060 China Division of Infectious Disease Brigham and Women 's Hospital and Department of Microbiology and Immunobiology Harvard Medical School Boston MA 02115 USA Beijing Genomics Institute Co. Ltd. Shenzhen 518083 China Department of Medical Oncology Affiliated Tumor Hospital of Guangzhou Medical University Guangzhou 510095 China Department of Oncology and Hematology The First Affiliated Hospital of Guangzhou Medical University Guangzhou 510120 China

The latent expression pattern of Epstein-Barr Virus （EBV）igenes in nasopharyngeal carcinoma （NPC） has been extensively investigated, and the expression of several lytic genes in NPC has been reported. However, comprehensive information through EBV transcriptome analysis in NPC is limited. We performed paired-end RNA-seq to systematically and comprehensively characterize the expression of EBV genes in NPC tissue and C666-1 NPC cell line, which consistently carries EBV. In addition to the transcripts restricted to type II latency infection, the type Ⅲ latency EBNA3s genes and a substantial number of lytic genes, such as BZLF1, BRLF1, and BMRF1, were detected through RNA-seq and were further verified in C666-1 cells and NPC tissue through real- time PCR. We also performed clustering analysis to classify NPC patient groups in terms of EBV gene expression, which presented two subtypes of NPC samples. Results revealed interesting patterns of EBV gene expression in NPC patients. This clustering was correlated with many signaling pathways, such as those related to heterotrimeric G-protein signaling, inflammation mediated by chemokine and cytokine signaling, ribosomes, protein metabolism, influenza infection, and ECM-receptor interaction. Our combined findings suggested that the expression of EBV genes in NPC is restricted not only to type II latency genes but also to type Ⅲ latency and lyric genes. This study provided further insights into the potential role of EBV in the development of NPC.

关键词： Epstein-Barr virus paired-end transcriptome sequencing latency genes lytic genes nasopharyngeal carcinoma

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