TY - JOUR
T1 - APOBEC3A associates with human papillomavirus genome integration in oropharyngeal cancers
AU - Kondo, S.
AU - Wakae, K.
AU - Wakisaka, N.
AU - Nakanishi, Y.
AU - Ishikawa, K.
AU - Komori, T.
AU - Moriyama-Kita, M.
AU - Endo, K.
AU - Murono, S.
AU - Wang, Z.
AU - Kitamura, K.
AU - Nishiyama, T.
AU - Yamaguchi, K.
AU - Shigenobu, S.
AU - Muramatsu, M.
AU - Yoshizaki, T.
N1 - Publisher Copyright:
© 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved 0950-9232/17.
PY - 2017/3/23
Y1 - 2017/3/23
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84989944799&partnerID=8YFLogxK
U2 - 10.1038/onc.2016.335
DO - 10.1038/onc.2016.335
M3 - 学術論文
C2 - 27694899
AN - SCOPUS:84989944799
SN - 0950-9232
VL - 36
SP - 1687
EP - 1697
JO - Oncogene
JF - Oncogene
IS - 12
ER -
