Sui Shuang, Jiao Zhen, Chen Hongxiang, Niyazi Mayinuer, Wang Lin
Department of Obstetrics and Gynecology, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang Uygur Autonomous Region 830001, P.R. China.
Oncol Lett. 2020 Aug;20(2):1752-1760. doi: 10.3892/ol.2020.11697. Epub 2020 Jun 5.
The present study aimed to investigate whether apolipoprotein B mRNA-editing enzyme catalytic polypeptides (A3) are involved in the regulation of cervical cancer development and human papilloma virus (HPV)16 sustained infection in Uighur females. Cervical tissues of Uygur patients with HPV16 with cervical lesions were collected. Expression levels of A3C, A3F and A3G were detected using reverse transcription-quantitative PCR and western blotting. A model of SiHa cells with high expression levels of A3C, A3F and A3G was constructed. Hypermutation was detected using the differential DNA denaturation PCR and positive samples were amplified and sequenced. There were significant differences in A3 expression levels in cervical lesions of different grades. A3C and A3F mRNA and protein expression in cervical cancer tissues were significantly lower, whereas the A3G mRNA and protein expression levels were significantly higher compared with the cervicitis and cervical intraepithelial neoplasia (CIN) I-III groups. Hypermutation rates were increased with cervical lesion development. C>T and G>A base substitutions were detected in all hypermutation samples and numbers of C>T and G>A base substitutions in single samples in the cervical cancer group were significantly higher compared with those in the CIN I-III and cervicitis groups. Following transfection of A3F and A3G, HPV E2 mRNA and protein expression levels were significantly decreased in SiHa cells. Numerous C>T and G>A base substitutions were detected in the HPV E2 gene in A3G and A3C overexpressing SiHa cells. A3 family proteins inhibit viral replication during HPV16 infection and regulate the HPV16 integration by inducing C>T and G>A hypermutations in the HPV16 E2 gene, thus affecting the cervical cancer pathogenesis and development.
本研究旨在探讨载脂蛋白B信使核糖核酸编辑酶催化多肽（A3）是否参与维吾尔族女性宫颈癌发生发展及人乳头瘤病毒（HPV）16持续感染的调控。收集维吾尔族HPV16阳性且伴有宫颈病变患者的宫颈组织。采用逆转录定量聚合酶链反应及蛋白质印迹法检测A3C、A3F和A3G的表达水平。构建A3C、A3F和A3G高表达的SiHa细胞模型。采用差异DNA变性聚合酶链反应检测高突变情况，并对阳性样本进行扩增和测序。不同级别宫颈病变中A3表达水平存在显著差异。与宫颈炎和宫颈上皮内瘤变（CIN）I - III组相比，宫颈癌组织中A3C和A3F的信使核糖核酸及蛋白质表达显著降低，而A3G的信使核糖核酸及蛋白质表达水平显著升高。高突变率随宫颈病变进展而增加。在所有高突变样本中均检测到C>T和G>A碱基替换，宫颈癌组单个样本中C>T和G>A碱基替换的数量显著高于CIN I - III组和宫颈炎组。转染A3F和A3G后，SiHa细胞中HPV E2信使核糖核酸和蛋白质表达水平显著降低。在A3G和A3C过表达的SiHa细胞的HPV E2基因中检测到大量C>T和G>A碱基替换。A3家族蛋白在HPV16感染期间抑制病毒复制，并通过诱导HPV16 E2基因中的C>T和G>A高突变来调控HPV16整合，从而影响宫颈癌的发病机制和发展。
