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中国西南地区HPV-16变异体中长控制区的遗传变异性及其功能意义

Genetic variability and functional implication of the long control region in HPV-16 variants in Southwest China.

作者信息

Xi Juemin, Chen Junying, Xu Miaoling, Yang Hongying, Luo Jia, Pan Yue, Wang Xiaodan, Qiu Lijuan, Yang Jiajia, Sun Qiangming

机构信息

Institute of Medical Biology, Chinese Academy of Medical Sciences, and Peking Union Medical College, Kunming, People's Republic of China.

Yunnan Key Laboratory of Vaccine Research & Development on Severe Infectious Diseases, Kunming, People's Republic of China.

出版信息

PLoS One. 2017 Aug 2;12(8):e0182388. doi: 10.1371/journal.pone.0182388. eCollection 2017.

Abstract

HPV-16 long control region (LCR) has been shown to be the most variable region of the HPV-16 genome and may play important roles in viral persistence and the development of cervical cancer. This study aimed to assess the risk of HPV-16 LCR variants for cervical cancer in women of Southwest China. 2146 cervical scrapings of volunteer outpatients and 74 cervical cancer tissues were screened.14 entire HPV-16 LCRs from asymptomatic carriers and 34 entire HPV-16 LCRs from cervical cancer patients were successfully amplified and sequenced to align to others described. 58 different point mutations were detected in 54 nucleotide sites of HPV-16 LCR. G7193T and G7521A variants, accounting for 100% of the infections, were predicted to locate at the binding site for FOXA1 and SOX9, respectively. A7730C variant which showed a high mutation frequency in cervical cancer was predicted to be a binding site for the cellular transcription factor PHOX2A. In addition, phylogenetic analysis displayed a high prevalence of A lineage in HPV-16 LCR in this Southwest China population. This study may help understanding of the intrinsic geographical relatedness and the correlations between LCR mutations and the development of carcinogenic lesions in Southwest China population. And it provides useful data for the further study of the biological function of HPV-16 LCR variants.

摘要

人乳头瘤病毒16型长控制区(LCR)已被证明是人乳头瘤病毒16型基因组中最具变异性的区域,可能在病毒持续存在和宫颈癌发生过程中发挥重要作用。本研究旨在评估中国西南地区女性人乳头瘤病毒16型LCR变异体导致宫颈癌的风险。对2146份志愿者门诊患者宫颈刮片和74份宫颈癌组织进行了筛查。成功扩增并测序了14份无症状携带者的完整人乳头瘤病毒16型LCR和34份宫颈癌患者的完整人乳头瘤病毒16型LCR,并与其他已描述的序列进行比对。在人乳头瘤病毒16型LCR的54个核苷酸位点检测到58种不同的点突变。G7193T和G7521A变异体分别占感染的100%,预计分别位于FOXA1和SOX9的结合位点。在宫颈癌中显示出高突变频率的A7730C变异体预计是细胞转录因子PHOX2A的结合位点。此外,系统发育分析显示在中国西南地区人群中,人乳头瘤病毒16型LCR中A谱系的流行率很高。本研究可能有助于了解中国西南地区人群中LCR突变与致癌病变发生之间的内在地理相关性及关联。并且它为进一步研究人乳头瘤病毒16型LCR变异体的生物学功能提供了有用的数据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc66/5540483/373b5b89acb0/pone.0182388.g001.jpg

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