APOBEC3A associates with human papillomavirus genome integration in oropharyngeal cancers
APOBEC3A associates with human papillomavirus genome integration in oropharyngeal cancers
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APOBEC3A 与口咽癌中人乳头瘤病毒基因组整合相关
DOI：
10.1038/onc.2016.335
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发表时间：
2017-03-01
期刊：
影响因子：
8
通讯作者：
Yoshizaki, T.
中科院分区：
文献类型：
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作者：
Kondo, S.;Wakae, K.;Yoshizaki, T.
在发达国家，人乳头瘤病毒（HPV）相关口咽癌的发病率一直在上升。我们最近发现，载脂蛋白B mRNA编辑催化多肽3（APOBEC 3，A3）家族的成员，这是抗病毒因子，可以诱导HPV DNA在体外的超突变。在本研究中，我们使用差异DNA变性PCR和下一代测序技术在口咽癌（OPC）活检样本中发现了许多HPV16基因组中的C至T和G至A超突变。A3在HPV 16阳性的OPCs中的表达比HPV阴性的OPCs更丰富，采用免疫组化和逆转录定量PCR进行评估。此外，干扰素上调A3在HPV 16阳性OPC细胞系。此外，HPV DNA的定量PCR分析表明，APOBEC3A（A3A）表达与HPV DNA的整合密切相关。这些结果表明，HPV 16感染可能上调A3A表达，从而增加病毒DNA整合的机会。A3A在HPV诱导的致癌作用进行了讨论。
The prevalence of human papillomavirus (HPV)-related oropharyngeal cancers has been increasing in developed countries. We recently demonstrated that members of the apolipoprotein B mRNA-editing catalytic polypeptide 3 (APOBEC3, A3) family, which are antiviral factors, can induce hypermutation of HPV DNA in vitro. In the present study, we found numerous C-to-T and G-to-A hypermutations in the HPV16 genome in oropharyngeal cancer (OPC) biopsy samples using differential DNA denaturation PCR and next-generation sequencing. A3s were more abundantly expressed in HPV16-positive OPCs than in HPV-negative, as assessed using immunohistochemistry and reverse transcription quantitative PCR. In addition, interferons upregulated A3s in an HPV16-positive OPC cell line. Furthermore, quantitative PCR analysis of HPV DNA suggests that APOBEC3A (A3A) expression is strongly correlated with the integration of HPV DNA. These results suggest that HPV16 infection may upregulate A3A expression, thereby increasing the chance of viral DNA integration. The role of A3A in HPV-induced carcinogenesis is discussed.