國家衛生研究院 NHRI:Item 3990099045/10783
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    题名: Epstein-Barr virus BRLF1 induces genomic instability and progressive malignancy in nasopharyngeal carcinoma cells
    作者: Huang, SY;Wu, CC;Cheng, YJ;Chou, SP;Jiang, YJ;Chu, KC;Tsai, CH;Lin, SF;Chen, JY
    贡献者: Institute of Molecular and Genomic Medicine;National Institute of Cancer Research
    摘要: 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.
    日期: 2017-09-05
    關聯: Oncotarget. 2017 Sep 5;8(45):78948-78964.
    Link to: http://dx.doi.org/10.18632/oncotarget.20695
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000412111300062
    显示于类别:[江運金] 期刊論文
    [陳振陽] 期刊論文
    [林素芳] 期刊論文

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