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Comprehensive profiling of Epstein-Barr virus-encoded miRNA species associated with specific latency types in tumor cells

Hong-Jie Yang1, Tie-Jun Huang2, Chang-Fu Yang34, Li-Xia Peng1, Ran-Yi Liu1, Guang-Da Yang1, Qiao-Qiao Chu6, Jia-Ling Huang5, Na Liu1, Hong-Bing Huang1, Zhen-Yu Zhu4, Chao-Nan Qian1* and Bi-Jun Huang1*

Author Affiliations

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 Nuclear Medicine, the second People’s Hospital of Shenzhen, Shenzhen 518038, China

3 Department of Cancer Chemotherapy, the People’s Hospital of Gaozhou, Guangzhou, Guangdong province 525200, China

4 Department of Biochemistry & Molecular Biology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou Guangdong province, P.R. China

5 Department of Medicine, Division of Infectious Diseases, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6073, USA

6 School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou People’s Republic of China

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Virology Journal 2013, 10:314  doi:10.1186/1743-422X-10-314

Published: 26 October 2013

Abstract

Background

Epstein-Barr virus (EBV) is an etiological cause of many human lymphocytic and epithelial malignancies. EBV expresses different genes that are associated with three latency types. To date, as many as 44 EBV-encoded miRNA species have been found, but their comprehensive profiles in the three types of latent infection that are associated with various types of tumors are not well documented.

Methods

In the present study, we utilized poly (A)-tailed quantitative real-time RT-PCR in combination with microarray analysis to measure the relative abundances of viral miRNA species in a subset of representative lymphoid and epithelial tumor cells with various EBV latency types.

Results

Our findings showed that the miR-BHRF1 and miR-BART families were expressed differentially in a tissue- and latency type-dependent manner. Specifically, in nasopharyngeal carcinoma (NPC) tissues and the EBV-positive cell line C666-1, the miR-BART family accounted for more than 10% of all detected miRNAs, suggesting that these miRNAs have important roles in maintaining latent EBV infections and in driving NPC tumorigenesis. In addition, EBV miRNA-based clustering analysis clearly distinguished between the three distinct EBV latency types, and our results suggested that a switch from type I to type III latency might occur in the Daudi BL cell line.

Conclusions

Our data provide a comprehensive profiling of the EBV miRNA transcriptome that is associated with specific tumor cells in the three types of latent EBV infection states. EBV miRNA species represent a cluster of non-encoding latency biomarkers that are differentially expressed in tumor cells and may help to distinguish between the different latency types.

Keywords:
Epstein-Barr virus; Viral microRNA; Latency types; Nasopharyngeal carcinoma; Burkitt’s lymphoma