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

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 

机构地区：[1]State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine and [2]Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou 510060, China [3]First Affiliated Hospital of Jinan University, Guangzhou 510630, China [4]Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou 510060, China [5]Division of Infectious Disease, Brigham and Women 's Hospital and Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA [6]Beijing Genomics Institute Co., Ltd., Shenzhen 518083, China [7]Department of Medical Oncology, Affiliated Tumor Hospital of Guangzhou Medical University, Guangzhou 510095, China [8]Department of Oncology and Hematology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China

出　　处：《Frontiers of Medicine》2016年第1期61-75,共15页医学前沿（英文版）

基　　金：This study was supported by 973 Program and 863 Program from the Ministry of Science and Technology of China （Nos. 2011CB504300 and 2015AA020931）, National Natural Science Foundation of China （Nos. 91440106, 91019015, and 81302037）, Ph.D. Startup of Guangzhou Medical University （No. 2012C65）, Guangzhou Science and Technology Planing Project （No. 2014J4100181）, and Young Teacher Training Program ofStm Yat-sen University （No. 13ykpy50）.

摘　　要：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.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 

分 类 号：Q786[生物学—分子生物学] S855.3[农业科学—临床兽医学]