PUBLICATION

Epstein-Barr virus BRLF1 induces genomic instability and progressive malignancy in nasopharyngeal carcinoma cells

Authors
Huang, S.Y., Wu, C.C., Cheng, Y.J., Chou, S.P., Jiang, Y.J., Chu, K.C., Tsai, C.H., Lin, S.F., Chen, J.Y.
ID
ZDB-PUB-171108-9
Date
2017
Source
Oncotarget   8: 78948-78964 (Journal)
Registered Authors
Chu, Kuo-Chang, Jiang, Yun-Jin
Keywords
BRLF1, Epstein–Barr virus, chromosome mis-segregation, genomic instability, nasopharyngeal carcinoma
MeSH Terms
none
PubMed
29108278 Full text @ Oncotarget
Abstract
Nasopharyngeal carcinoma (NPC) is a serious health problem in China and Southeast Asia. Relapse is the major cause of mortality, but mechanisms of relapse are mysterious. Epstein-Barr virus (EBV) reactivation and host genomic instability (GI) have correlated with NPC development. Previously, we reported that lytic early genes DNase and BALF3 induce genetic alterations and progressive malignancy in NPC cells, implying lytic proteins may be required for NPC relapse. In this study, we show that immediate early gene BRLF1 induces chromosome mis-segregation and genomic instability in the NPC cells. Similar phenomenon was also demonstrated in 293 and zebrafish embryonic cells. BRLF1 nuclear localization signal (NLS) mutant still induced genomic instability and inhibitor experiments revealed that BRLF1 interferes with chromosome segregation and induces genomic instability by activating Erk signaling. Furthermore, the chromosome aberrations and tumorigenic features of NPC cells were significantly increased with the rounds of BRLF1 expression, and these cells developed into larger tumor nodules in mice. Therefore, BRLF1 may be the important factor contributing to NPC relapse and targeting BRLF1 may benefit patients.
Genes / Markers
Figures
Show all Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping