Open AccessEBV‐LMP1 induces APOBEC3s and mitochondrial DNA hypermutation in nasopharyngeal cancer
Author(s) -
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,
MoriyamaKita Makiko,
Ishikawa Kazuya,
Nakanishi Yosuke,
Endo Kazuhira,
Muramatsu Masamichi,
Yoshizaki Tomokazu
Publication year - 2020
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.3357
Subject(s) - somatic hypermutation , biology , mitochondrial dna , cancer research , oncogene , mutation , genetics , gene , epstein–barr virus , genome instability , virology , virus , dna damage , dna , cell cycle , antibody , b cell
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.