小狗阅读会员会员
有解析的医学SCI阅读工具

扫码登录小狗阅读

阅读SCI医学文献

Human papillomavirus 58E7 T20I/G63S variant isolated from an East Asian population possesses high oncogenicity.

从东亚人群中分离的人乳头瘤病毒 58E7 T20I/G63S 变异体具有高致癌性。

  • 影响因子:4.02
  • DOI:10.1128/JVI.00090-20
  • 作者列表:"Boon SS","Xia C","Lim JY","Chen Z","Law PTY","Yeung ACM","Thomas M","Banks L","Chan PKS
  • 发表时间:2020-01-29
Abstract

:Human papillomavirus (HPV) type 58 is the third most commonly detected HPV type in cervical cancer among Eastern Asians. Our previous international epidemiological studies revealed that a HPV58E7 natural variant, T20I/G63S (designated as V1), was associated with a higher risk of cervical cancer. We recently showed that V1 possesses a greater ability to immortalise and transform primary cells, as well as degrading pRB more effectively than the prototype and other common variants. In this study, we performed a series of phenotypic and molecular assays using physiologically relevant in vitro and in vivo models to compare the oncogenicity of V1 with that of the prototype and other common natural variants. Through activation of AKT and K-Ras/ERK signalling pathways, V1 consistently showed greater oncogenicity compared with prototype and other variants, as demonstrated by increased cell proliferation, migration and invasion, as well as induction of larger tumours in athymic nude mice. This study complements our previous epidemiological and molecular observations pinpointing the higher oncogenicity of V1 compared with prototype and all other common variants. Since V1 is more commonly found in Eastern Asia, our report provides insight into the design of HPV-screening assays and selection of components for HPV vaccines in this region.IMPORTANCE Epidemiological studies have revealed that a wild type variant of HPV58 carrying an E7 variation, T20I/G63S (V1), is associated with a higher risk of cervical cancer. We previously reported that this increased oncogenicity could be the result of its greater ability to degrade pRB, thereby leading to an increased ability to grow in an anchorage-independent manner. In addition to this, this report further showed that this HPV variant induced activation of AKT and K-Ras/ERK signalling pathways, thereby, explaining its genuine oncogenicity in promoting cell proliferation, migration, invasion, and formation of tumours, all to a greater extent than prototype HPV58 and other common variants.

摘要

: 人乳头瘤病毒 (HPV) 58 型是东亚人宫颈癌中第三常见的 HPV 类型。我们以前的国际流行病学研究发现,HPV58E7 自然变异体 T20I/G63S (命名为 V1) 与宫颈癌的高风险相关。我们最近发现,与原型和其他常见变体相比,V1 具有更大的永生化和转化原代细胞的能力,以及更有效地降解 pRB 的能力。在本研究中,我们使用生理相关的体外和体内模型进行了一系列表型和分子检测,比较 V1 与原型和其他常见天然变异体的致癌性。通过激活 AKT 和 K-Ras/ERK 信号通路,与原型和其他变体相比,V1 始终表现出更大的致癌性,表现为细胞增殖、迁移和侵袭增加, 以及在无胸腺裸鼠中诱导较大的肿瘤。本研究补充了我们以前的流行病学和分子观察,指出与原型和所有其他常见变体相比,V1 的致癌性更高。由于 V1 在东亚更常见,我们的报告提供了该地区 HPV 筛查试验的设计和 HPV 疫苗组分的选择。重要性流行病学研究发现,携带 E7 变异的 HPV58 野生型变异体 T20I/G63S (V1) 与宫颈癌的高风险相关。我们之前报道过,这种致癌性的增加可能是其降解 pRB 的能力更强的结果,从而导致以不依赖锚定的方式生长的能力增加。除此之外,本报告进一步表明,这种 HPV 变体诱导 AKT 和 K-Ras/ERK 信号通路的激活,从而解释其在促进细胞增殖、迁移、侵袭和肿瘤的形成,都比原型 HPV58 和其他常见变异更大。

关键词:
阅读人数:5人
下载该文献
小狗阅读

帮助医生、学生、科研工作者解决SCI文献找不到、看不懂、阅读效率低的问题。提供领域精准的SCI文献,通过多角度解析提高文献阅读效率,从而使用户获得有价值研究思路。

相关文献
影响因子:2.69
发表时间:2020-01-29
DOI:10.1016/j.bbrc.2019.11.079
作者列表:["Zhang Z","Chen F","Li S","Guo H","Xi H","Deng J","Han Q","Zhang W"]

METHODS::Altered aerobic glycolysis is an important feature of cancer cell energy metabolism, known as the Warburg effect. Cervical cancer is one of the most common causes of cancer death in females. However, the roles of aerobic glycolysis in the development of cervical cancer are still poorly defined. Here, we identified a transcription factor (TF), ETS-related gene (ERG), as a new regulator of cancer progression and the glycolysis process in cervical cancer. In this study, we found that ectopic expression of ERG enhanced the capacity of aerobic glycolysis and increased glucose uptake, lactate production, and ATP generation. ERG overexpression increased and ERG knockdown decreased the anchorage independent cell growth and cell invasion in cervical cancer cells. Mechanistically, we propose that ERG regulates the expression of hexokinase 2 (HK2) and phosphoglycerate kinase 1 (PGK1) in the glycolytic pathway by directly binding to their promoters. A gain-of-function study showed that the knockdown or overexpression of HK2 and PGK1 abolished the increased or decreased aerobic glycolysis and cervical cancer progression induced by stable ectopic expression or depletion of ERG, respectively. Taken together, our findings suggest that ERG plays a potential role in the progression of cervical cancer, and could serve as a novel biomarker and potential therapeutic target in cervical cancer.

翻译标题与摘要 下载文献
影响因子:3.18
发表时间:2020-01-29
来源期刊:Vaccine
DOI:10.1016/j.vaccine.2019.11.019
作者列表:["Shilling H","Murray G","Brotherton JML","Hawkes D","Saville M","Sivertsen T","Chambers I","Roberts J","Farnsworth A","Garland SM","Hocking JS","Kaldor J","Guy R","Atchison S","Costa AM","Molano M","Machalek DA"]

METHODS:INTRODUCTION:Australia has recently implemented major changes in cervical cancer prevention policies including introduction of primary human papillomavirus (HPV) screening starting at age 25, and replacement of the quadrivalent HPV vaccine with the nonavalent vaccine in the national school-based program. We assessed the feasibility and utility of conducting HPV testing in residual clinical specimens submitted for routine Chlamydia trachomatis screening, as a means of tracking HPV vaccine program impact among young sexually active women. METHODS:De-identified residual specimens from women aged 16-24 years submitted for chlamydia testing were collected from three pathology laboratories in Victoria and New South Wales. Limited demographic information, and chlamydia test results were also collected. Patient identifiers were sent directly from the laboratories to the National HPV Vaccination Program Register, to obtain HPV vaccination histories. Samples underwent HPV genotyping using Seegene Anyplex II HPV 28 assay. RESULTS:Between April and July 2018, 362 residual samples were collected, the majority (60.2%) of which were cervical swabs. Demographic data and vaccination histories were received for 357 (98.6%) women (mean age 21.8, SD 2.0). Overall, 65.6% of women were fully vaccinated, 9.8% partially, and 24.7% unvaccinated. The majority (86.0%) resided in a major city, 35.9% were classified in the upper quintile of socioeconomic advantage and chlamydia positivity was 7.8%.The prevalence of quadrivalent vaccine-targeted types (HPV6/11/16/18) was 2.8% (1.5-5.1%) overall with no differences by vaccination status (p = 0.729). The prevalence of additional nonavalent vaccine-targeted types (HPV31/33/45/52/58) was 19.3% (15.6-23.8%). One or more oncogenic HPV types were detected in 46.8% (95% CI 41.6-52.0%) of women. CONCLUSIONS:HPV testing of residual chlamydia specimens provides a simple, feasible method for monitoring circulating genotypes. Applied on a larger scale this method can be utilised to obtain a timely assessment of nonavalent vaccine impact among young women not yet eligible for cervical screening.

翻译标题与摘要 下载文献
影响因子:4.02
发表时间:2020-01-29
来源期刊:Journal of virology
DOI:10.1128/JVI.00090-20
作者列表:["Boon SS","Xia C","Lim JY","Chen Z","Law PTY","Yeung ACM","Thomas M","Banks L","Chan PKS"]

METHODS::Human papillomavirus (HPV) type 58 is the third most commonly detected HPV type in cervical cancer among Eastern Asians. Our previous international epidemiological studies revealed that a HPV58E7 natural variant, T20I/G63S (designated as V1), was associated with a higher risk of cervical cancer. We recently showed that V1 possesses a greater ability to immortalise and transform primary cells, as well as degrading pRB more effectively than the prototype and other common variants. In this study, we performed a series of phenotypic and molecular assays using physiologically relevant in vitro and in vivo models to compare the oncogenicity of V1 with that of the prototype and other common natural variants. Through activation of AKT and K-Ras/ERK signalling pathways, V1 consistently showed greater oncogenicity compared with prototype and other variants, as demonstrated by increased cell proliferation, migration and invasion, as well as induction of larger tumours in athymic nude mice. This study complements our previous epidemiological and molecular observations pinpointing the higher oncogenicity of V1 compared with prototype and all other common variants. Since V1 is more commonly found in Eastern Asia, our report provides insight into the design of HPV-screening assays and selection of components for HPV vaccines in this region.IMPORTANCE Epidemiological studies have revealed that a wild type variant of HPV58 carrying an E7 variation, T20I/G63S (V1), is associated with a higher risk of cervical cancer. We previously reported that this increased oncogenicity could be the result of its greater ability to degrade pRB, thereby leading to an increased ability to grow in an anchorage-independent manner. In addition to this, this report further showed that this HPV variant induced activation of AKT and K-Ras/ERK signalling pathways, thereby, explaining its genuine oncogenicity in promoting cell proliferation, migration, invasion, and formation of tumours, all to a greater extent than prototype HPV58 and other common variants.

关键词: 暂无
翻译标题与摘要 下载文献
方向

复制标题
发送后即可在该邮箱或我的下载查看该文献
发送
该文献默认存储到我的下载

科研福利

报名咨询

建议反馈
问题标题:
联系方式:
电子邮件:
您的需求: