APOBEC3A possesses anticancer and antiviral effects by differential inhibition of HPV E6 and E7 expression on cervical cancer.

IF 0.2 Q4 MEDICINE, RESEARCH & EXPERIMENTAL International journal of clinical and experimental medicine Pub Date : 2015-07-15 eCollection Date: 2015-01-01
Shan Chen, Xiao Li, Junpu Qin, Yuan Chen, Longyang Liu, Dongqing Zhang, Minyi Wang, Maocai Wang, Dikai Zhang
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Abstract

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.

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APOBEC3A通过差异抑制HPV E6和E7在宫颈癌中的表达而具有抗癌和抗病毒作用。
子宫颈癌是全世界妇女中第二大常见癌症,也是发展中国家死亡的主要原因。持续感染hpv亚型,称为“高危hpv”,包括HPV16和HPV18,是宫颈癌的主要原因。载脂蛋白B mRNA编辑酶,催化多肽样蛋白(APOBEC)家族蛋白是一组在单链DNA/RNA中催化胞苷(C)脱氨为尿嘧啶(U)的细胞酶,在宿主先天免疫系统中起抗病毒因子的作用。最近的研究表明,APOBEC3A可以限制某些DNA病毒,包括人乳头瘤病毒。在本研究中,我们证实了APOBEC3A在宫颈癌组织中的表达降低。APOBEC3A通过胞苷脱氨酶抑制宫颈细胞的增殖、迁移和侵袭,促进细胞凋亡。此外,APOBEC3A对HPV16-E6、HPV16-E7和HPV18-E6的抑制作用依赖于胞苷脱氨酶,但对HPV18-E7无影响。因此,我们认为,在宫颈癌细胞中,APOBEC3A的表达通过胞苷脱氨酶对HPV E6和E7表达的差异抑制而具有抗癌和抗病毒作用。
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