Chen Shan, Li Xiao, Qin Junpu, Chen Yuan, Liu Longyang, Zhang Dongqing, Wang Minyi, Wang Maocai, Zhang Dikai
Department of Gynaecology and Obstetrics, The Sixth Affiliated Hospital of Sun Yat-Sen University Guangzhou, China.
Int J Clin Exp Med. 2015 Jul 15;8(7):10548-57. eCollection 2015.
Cervical cancer is the second most common cancer among women worldwide and is the leading cause of deaths in developing countries. Persistent infections with a subset of HPVs, called "high-risk HPVs", including HPV16 and HPV18, are the primary cause of cervical cancer. The apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like (APOBEC) family of proteins is a group of cellular enzymes that catalyze the deamination of cytidine (C) to uracil (U) in single-stranded DNA/RNA, and functions as antiviral factors in the innate immune system of the host. Recent studies have shown that APOBEC3A could restrict certain DNA viruses, including HPVs. In this study, we confirmed that the expression of APOBEC3A was decreased in cervical cancer tissues. Furthermore, APOBEC3A inhibited the cervical cells proliferation, migration as well as invasion, and promoted apoptosis depend on cytidine deaminase. In addition, APOBEC3A decreased HPV16-E6, HPV16-E7 and HPV18-E6 depend on cytidine deaminase, but no effect on HPV18-E7. Therefore, we believe that, in cervical cancer cells, the expression of APOBEC3A possesses anticancer and antiviral effects by differential inhibition of HPV E6 and E7 expression depend on cytidine deaminase.
宫颈癌是全球女性中第二常见的癌症,也是发展中国家女性死亡的主要原因。持续感染一部分被称为“高危型人乳头瘤病毒(HPV)”的病毒,包括HPV16和HPV18,是宫颈癌的主要病因。载脂蛋白B信使核糖核酸编辑酶催化多肽样(APOBEC)蛋白家族是一组细胞酶,可催化单链DNA/RNA中的胞嘧啶(C)脱氨生成尿嘧啶(U),并在宿主的先天免疫系统中作为抗病毒因子发挥作用。最近的研究表明,APOBEC3A可以限制某些DNA病毒,包括HPV。在本研究中,我们证实宫颈癌组织中APOBEC3A的表达降低。此外,APOBEC3A通过胞嘧啶脱氨酶抑制宫颈细胞的增殖、迁移和侵袭,并促进细胞凋亡。此外,APOBEC3A通过胞嘧啶脱氨酶降低HPV16-E6、HPV16-E7和HPV18-E6的表达,但对HPV18-E7没有影响。因此,我们认为,在宫颈癌细胞中,APOBEC3A的表达通过依赖胞嘧啶脱氨酶对HPV E6和E7表达的差异抑制而具有抗癌和抗病毒作用。