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Epstein–Barr virus BRLF1 induces genomic instability and progressive malignancy in nasopharyngeal carcinoma cells
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 repo...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5668011/ https://www.ncbi.nlm.nih.gov/pubmed/29108278 http://dx.doi.org/10.18632/oncotarget.20695 |
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author | Huang, Sheng-Yen Wu, Chung-Chun Cheng, Yu-Jhen Chou, Sheng-Ping Jiang, Yun-Jin Chu, Kuo-Chang Tsai, Ching-Hwa Lin, Su-Fang Chen, Jen-Yang |
author_facet | Huang, Sheng-Yen Wu, Chung-Chun Cheng, Yu-Jhen Chou, Sheng-Ping Jiang, Yun-Jin Chu, Kuo-Chang Tsai, Ching-Hwa Lin, Su-Fang Chen, Jen-Yang |
author_sort | Huang, Sheng-Yen |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5668011 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-56680112017-11-04 Epstein–Barr virus BRLF1 induces genomic instability and progressive malignancy in nasopharyngeal carcinoma cells Huang, Sheng-Yen Wu, Chung-Chun Cheng, Yu-Jhen Chou, Sheng-Ping Jiang, Yun-Jin Chu, Kuo-Chang Tsai, Ching-Hwa Lin, Su-Fang Chen, Jen-Yang Oncotarget Research Paper 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. Impact Journals LLC 2017-09-05 /pmc/articles/PMC5668011/ /pubmed/29108278 http://dx.doi.org/10.18632/oncotarget.20695 Text en Copyright: © 2017 Huang et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Huang, Sheng-Yen Wu, Chung-Chun Cheng, Yu-Jhen Chou, Sheng-Ping Jiang, Yun-Jin Chu, Kuo-Chang Tsai, Ching-Hwa Lin, Su-Fang Chen, Jen-Yang Epstein–Barr virus BRLF1 induces genomic instability and progressive malignancy in nasopharyngeal carcinoma cells |
title | Epstein–Barr virus BRLF1 induces genomic instability and progressive malignancy in nasopharyngeal carcinoma cells |
title_full | Epstein–Barr virus BRLF1 induces genomic instability and progressive malignancy in nasopharyngeal carcinoma cells |
title_fullStr | Epstein–Barr virus BRLF1 induces genomic instability and progressive malignancy in nasopharyngeal carcinoma cells |
title_full_unstemmed | Epstein–Barr virus BRLF1 induces genomic instability and progressive malignancy in nasopharyngeal carcinoma cells |
title_short | Epstein–Barr virus BRLF1 induces genomic instability and progressive malignancy in nasopharyngeal carcinoma cells |
title_sort | epstein–barr virus brlf1 induces genomic instability and progressive malignancy in nasopharyngeal carcinoma cells |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5668011/ https://www.ncbi.nlm.nih.gov/pubmed/29108278 http://dx.doi.org/10.18632/oncotarget.20695 |
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