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.
Choy
Elizabeth Yee-Wai
EY
Department of Biochemistry, The University of Hong Kong, Pokfulam, Hong Kong.
Siu
Kam-Leung
KL
Kok
Kin-Hang
KH
Lung
Raymond Wai-Ming
RW
Tsang
Chi Man
CM
To
Ka-Fai
KF
Kwong
Dora Lai-Wan
DL
Tsao
Sai Wah
SW
Jin
Dong-Yan
DY
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