An Epstein-Barr virus-encoded microRNA targets PUMA to promote host cell survival.
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 approximately 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.
Department of Biochemistry, The University of Hong Kong, Pokfulam, Hong Kong.
Elizabeth Yee-Wai
EY
Choy
Kam-Leung
KL
Siu
Kin-Hang
KH
Kok
Raymond Wai-Ming
RW
Lung
Chi Man
CM
Tsang
Ka-Fai
KF
To
Dora Lai-Wan
DL
Kwong
Sai Wah
SW
Tsao
Dong-Yan
DY
Jin
D017209:Apoptosis / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D015153:Blotting, Western; D002460:Cell Line; D002470:Cell Survival / Q000235:genetics* / Q000502:physiology; D019295:Computational Biology; D017931:DNA Primers / Q000235:genetics; D005786:Gene Expression Regulation / Q000235:genetics*; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D020287:In Situ Nick-End Labeling; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D010957:Plasmids / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000378:metabolism*
D051017:Apoptosis Regulatory Proteins; C438378:BBC3 protein, human; D017931:DNA Primers; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins