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Front Med. 2016 Mar;10(1):61-75. doi: 10.1007/s11684-016-0436-0. Epub 2016 Mar 11.

Comprehensive profiling of EBV gene expression in nasopharyngeal carcinoma through paired-end transcriptome sequencing.

Hu L1,2,3, Lin Z1,2, Wu Y1, Dong J1,2, Zhao B4, Cheng Y5, Huang P1,6, Xu L1,7, Xia T1,2, Xiong D1,2, Wang H1,2, Li M1,2, Guo L1,6, Kieff E4, Zeng Y1,2, Zhong Q8,9, Zeng M10,11.

Author information

1
State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China.
2
Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China.
3
Department of Medical Oncology, Affiliated Tumor Hospital of Guangzhou Medical University, Guangzhou, 510095, China.
4
Division of Infectious Disease, Brigham and Women's Hospital and Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA, 02115, USA.
5
Beijing Genomics Institute Co., Ltd., Shenzhen, 518083, China.
6
Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China.
7
Department of Oncology and Hematology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, China.
8
State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China. zhongqian@sysucc.org.cn.
9
Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China. zhongqian@sysucc.org.cn.
10
State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China. zengmsh@mail.sysu.edu.cn.
11
Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China. zengmsh@mail.sysu.edu.cn.

Abstract

The latent expression pattern of Epstein-Barr Virus (EBV) genes 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 realtime 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 lytic genes. This study provided further insights into the potential role of EBV in the development of NPC.

KEYWORDS:

Epstein-Barr virus; latency genes; lytic genes; nasopharyngeal carcinoma; paired-end transcriptome sequencing

PMID:
26969667
DOI:
10.1007/s11684-016-0436-0
[Indexed for MEDLINE]

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