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EBV‐LMP1 induces APOBEC3s and mitochondrial DNA hypermutation in nasopharyngeal cancer
An Epstein‐Barr virus (EBV)—encoded latent membrane protein 1 (LMP1) is a principal oncogene that plays a pivotal role in EBV‐associated malignant tumors including nasopharyngeal cancer (NPC). Recent genomic landscape studies revealed that NPC also contained many genomic mutations, suggesting the ro...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7571841/ https://www.ncbi.nlm.nih.gov/pubmed/32815637 http://dx.doi.org/10.1002/cam4.3357 |
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author | Wakae, Kousho Kondo, Satoru Pham, Hai Thanh Wakisaka, Naohiro Que, Lusheng Li, Yingfang Zheng, Xin Fukano, Kento Kitamura, Kouichi Watashi, Koichi Aizaki, Hideki Ueno, Takayoshi Moriyama‐Kita, Makiko Ishikawa, Kazuya Nakanishi, Yosuke Endo, Kazuhira Muramatsu, Masamichi Yoshizaki, Tomokazu |
author_facet | Wakae, Kousho Kondo, Satoru Pham, Hai Thanh Wakisaka, Naohiro Que, Lusheng Li, Yingfang Zheng, Xin Fukano, Kento Kitamura, Kouichi Watashi, Koichi Aizaki, Hideki Ueno, Takayoshi Moriyama‐Kita, Makiko Ishikawa, Kazuya Nakanishi, Yosuke Endo, Kazuhira Muramatsu, Masamichi Yoshizaki, Tomokazu |
author_sort | Wakae, Kousho |
collection | PubMed |
description | An Epstein‐Barr virus (EBV)—encoded latent membrane protein 1 (LMP1) is a principal oncogene that plays a pivotal role in EBV‐associated malignant tumors including nasopharyngeal cancer (NPC). Recent genomic landscape studies revealed that NPC also contained many genomic mutations, suggesting the role of LMP1 as a driver gene for the induction of these genomic mutations. Nonetheless, its exact mechanism has not been investigated. In this study, we report that LMP1 alters the expression profile of APOBEC3s(A3s), host deaminases that introduce consecutive C‐to‐U mutations (hypermutation). In vitro, LMP1 induces APOBEC3B (A3B) and 3F(A3F), in a nasopharyngeal cell line, AdAH. Overexpression of LMP1, A3B, or A3F induces mtDNA hypermutation, which is also detectable from NPC specimens. Expression of LMP1 and A3B in NPC was correlated with neck metastasis. These results provide evidence as to which LMP1 induces A3s and mtDNA hypermutation, and how LMP1 facilitates metastasis is also discussed. |
format | Online Article Text |
id | pubmed-7571841 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-75718412020-10-23 EBV‐LMP1 induces APOBEC3s and mitochondrial DNA hypermutation in nasopharyngeal cancer Wakae, Kousho Kondo, Satoru Pham, Hai Thanh Wakisaka, Naohiro Que, Lusheng Li, Yingfang Zheng, Xin Fukano, Kento Kitamura, Kouichi Watashi, Koichi Aizaki, Hideki Ueno, Takayoshi Moriyama‐Kita, Makiko Ishikawa, Kazuya Nakanishi, Yosuke Endo, Kazuhira Muramatsu, Masamichi Yoshizaki, Tomokazu Cancer Med Cancer Biology An Epstein‐Barr virus (EBV)—encoded latent membrane protein 1 (LMP1) is a principal oncogene that plays a pivotal role in EBV‐associated malignant tumors including nasopharyngeal cancer (NPC). Recent genomic landscape studies revealed that NPC also contained many genomic mutations, suggesting the role of LMP1 as a driver gene for the induction of these genomic mutations. Nonetheless, its exact mechanism has not been investigated. In this study, we report that LMP1 alters the expression profile of APOBEC3s(A3s), host deaminases that introduce consecutive C‐to‐U mutations (hypermutation). In vitro, LMP1 induces APOBEC3B (A3B) and 3F(A3F), in a nasopharyngeal cell line, AdAH. Overexpression of LMP1, A3B, or A3F induces mtDNA hypermutation, which is also detectable from NPC specimens. Expression of LMP1 and A3B in NPC was correlated with neck metastasis. These results provide evidence as to which LMP1 induces A3s and mtDNA hypermutation, and how LMP1 facilitates metastasis is also discussed. John Wiley and Sons Inc. 2020-08-20 /pmc/articles/PMC7571841/ /pubmed/32815637 http://dx.doi.org/10.1002/cam4.3357 Text en © 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Cancer Biology Wakae, Kousho Kondo, Satoru Pham, Hai Thanh Wakisaka, Naohiro Que, Lusheng Li, Yingfang Zheng, Xin Fukano, Kento Kitamura, Kouichi Watashi, Koichi Aizaki, Hideki Ueno, Takayoshi Moriyama‐Kita, Makiko Ishikawa, Kazuya Nakanishi, Yosuke Endo, Kazuhira Muramatsu, Masamichi Yoshizaki, Tomokazu EBV‐LMP1 induces APOBEC3s and mitochondrial DNA hypermutation in nasopharyngeal cancer |
title | EBV‐LMP1 induces APOBEC3s and mitochondrial DNA hypermutation in nasopharyngeal cancer |
title_full | EBV‐LMP1 induces APOBEC3s and mitochondrial DNA hypermutation in nasopharyngeal cancer |
title_fullStr | EBV‐LMP1 induces APOBEC3s and mitochondrial DNA hypermutation in nasopharyngeal cancer |
title_full_unstemmed | EBV‐LMP1 induces APOBEC3s and mitochondrial DNA hypermutation in nasopharyngeal cancer |
title_short | EBV‐LMP1 induces APOBEC3s and mitochondrial DNA hypermutation in nasopharyngeal cancer |
title_sort | ebv‐lmp1 induces apobec3s and mitochondrial dna hypermutation in nasopharyngeal cancer |
topic | Cancer Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7571841/ https://www.ncbi.nlm.nih.gov/pubmed/32815637 http://dx.doi.org/10.1002/cam4.3357 |
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