The Journal of Experimental Medicine
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Published online
doi:10.1084/jem.20072581
The Journal of Experimental Medicine, Vol. 205, No. 11, 2551-2560
The Rockefeller University Press, 0022-1007 $30.00
© Choy et al.
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ARTICLE

An Epstein-Barr virus–encoded microRNA targets PUMA to promote host cell survival

Elizabeth Yee-Wai Choy1, Kam-Leung Siu1, Kin-Hang Kok1, Raymond Wai-Ming Lung4, Chi Man Tsang2, Ka-Fai To4, Dora Lai-Wan Kwong3, Sai Wah Tsao2, and Dong-Yan Jin1

1 Department of Biochemistry, 2 Department of Anatomy, and 3 Department of Clinical Oncology, The University of Hong Kong, Pokfulam, Hong Kong
4 Department of Anatomical and Cellular Pathology, State Key Laboratory in Oncology in South China, Li Ka Shing Institute of Health Science, Prince of Wales Hospital, Chinese University of Hong Kong, Shatin, New Territories, Hong Kong

CORRESPONDENCE Dong-Yan Jin: dyjin{at}hkucc.hku.hk

Epstein-Barr virus (EBV) is a herpesvirus associated with nasopharyngeal carcinoma (NPC), gastric carcinoma (GC), and other malignancies. EBV is the first human virus found to express microRNAs (miRNAs), the functions of which remain largely unknown. We report on the regulation of a cellular protein named p53 up-regulated modulator of apoptosis (PUMA) by an EBV miRNA known as miR-BART5, which is abundantly expressed in NPC and EBV-GC cells. Modulation of PUMA expression by miR-BART5 and anti–miR-BART5 oligonucleotide was demonstrated in EBV-positive cells. In addition, PUMA was found to be significantly underexpressed in ~60% of human NPC tissues. Although expression of miR-BART5 rendered NPC and EBV-GC cells less sensitive to proapoptotic agents, apoptosis can be triggered by depleting miR-BART5 or inducing the expression of PUMA. Collectively, our findings suggest that EBV encodes an miRNA to facilitate the establishment of latent infection by promoting host cell survival.


Abbreviations used: EBER, EBV-encoded small RNA; EBV, Epstein-Barr virus; GC, gastric carcinoma; miRNA, microRNA; NPC, nasopharyngeal carcinoma; PARP, poly (ADP-ribose) polymerase; PUMA, p53 up-regulated modulator of apoptosis; siPUMA, small interfering RNA against PUMA; TUNEL, terminal deoxynucleotidyl transferase–mediated dUTP-biotin nick end labeling; UTR, untranslated region.

© 2008 Choy et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).


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