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About the Authors:
Shu-Jen Chen
Affiliations Department of Life Science, Chang Gung University, Taoyuan, Taiwan, Republic of China, Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan, Republic of China
Gian-Hung Chen
Affiliation: Department of Life Science, Chang Gung University, Taoyuan, Taiwan, Republic of China
Yi-Hsuan Chen
Affiliation: Department of Life Science, Chang Gung University, Taoyuan, Taiwan, Republic of China
Cheng-Yuan Liu
Affiliation: Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan, Republic of China
Kai-Ping Chang
Affiliation: Department of Otolaryngology, Chang Gung Memorial Hospital at Lin-Kou, Taoyuan, Taiwan, Republic of China
Yu-Sun Chang
Affiliation: Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan, Republic of China
Hua-Chien Chen
* E-mail: [email protected]
Affiliations Department of Life Science, Chang Gung University, Taoyuan, Taiwan, Republic of China, Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan, Republic of China
Introduction
A unique feature of nasopharyngeal carcinoma (NPC) is its strong association with Epstein-Barr Virus (EBV) [1]. EBV genome can be detected in all cases of NPC, suggesting that products of EBV genome are involved in the pathogenesis of this malignancy. In addition to EBV-encoded protein-coding genes such as EBNA1 and LMP1, latently infected NPC cells and tissues also express high levels of non-coding EBV RNAs, including EBER1, EBER2 and multiple microRNAs (miRNAs) [2], [3], [4], [5]. EBV miRNAs were first identified by Pfeffer et al. via cloning of small RNAs from a Burkitt's lymphoma cell line latently infected with EBV [6]. The authors identified six mature miRNAs derived from five miRNA precursors in the EBV genome. Grundhoff et al. subsequently identified 18 new precursors that produce 22 mature miRNAs in EBV-infected Jijoye and BJAB cells by combining computational and microarray approach [7]. Cai et al. also identified additional EBV miRNAs from EBV-positive BC-1 cells and demonstrated that the EBV miRNAs were conserved during lymphocryptovirus evolution [8]. Recently, Zhu et al. used the Roche 454 system to sequence ∼2,000 reads of EBV miRNAs in NPC tissues and discovered five novel mature EBV miRNAs [9]. To date, a total of 25 EBV miRNA precursors with 44 mature miRNAs have been reported [10].
These EBV miRNA precursors are clustered in two regions of the EBV genome. Three precursors (miR-BHRF1-1 to miR-BHRF1-3) with four mature miRNAs are located within the mRNA...