来自HIV-1感染的免疫细胞的副质信号重新编程宫癌途径
Charles Ochieng' Olwal1,2, Ujjwal Rathore3,4, Sara Makanani5,6,7
1West African Centre for Cell Biology of Infectious Pathogens (WACCBIP), College of Basic and Applied Sciences, University of Ghana, Accra, Ghana.
bioRxiv : the preprint server for biology
|July 15, 2025
概括
人类乳头瘤病毒 (HPV) 导致子宫癌. 患有HPV和人类免疫缺陷病毒1型 (HIV-1) 的妇女患癌症的风险更高,因为HIV-1会改变宫细胞信号通路,这表明PI3K通路是治疗点.
科学领域:
- 在瘤学瘤学.
- 病毒学 病毒学
- 免疫学 免疫学 免疫学
背景情况:
- 持续的人类乳头瘤病毒 (HPV) 感染是宫癌的主要原因.
- 同时感染HPV和人类免疫缺陷病毒1型 (HIV-1) 显著增加子宫癌的风险,即使在治疗.
- 艾滋病毒-1病毒影响子宫细胞信号传递的机制尚不清楚.
研究的目的:
- 研究HIV-1感染如何改变宫细胞中的信号通路.
- 确定将HIV-1与子宫癌风险增加联系在一起的分子机制.
- 探索与艾滋病毒相关的宫癌的潜在治疗点.
主要方法:
- 全球转录组学分析肯尼亚妇女的宫抽样,分层分为HPV,HIV-1和癌症状况.
- 全球质谱 (MS) 蛋白质组的宫细胞暴露在艾滋病毒-1感染的CD4+T细胞分泌体.
- 对转录基因和蛋白质基因数据的综合网络分析.
- 蛋白质组学MS分析以确认通路激活.
主要成果:
- 感染HIV-1的女性在非癌性宫上皮细胞中表现出类似癌症的基因表达模式.
- 蛋白质组分析显示了改变的MAPK,PI3K-AKT和β-catenin信号通路.
- 在患者样本和细胞培养中,IRS-1和干扰素刺激基因都被上调.
- 在暴露于HIV-1感染T细胞介质的宫细胞中证实了PI3K-AKT通路的激活.
结论:
- 艾滋病毒-1感染通过膜机制重塑宫细胞信号传递.
- PI3K-AKT通路是HIV-1对子宫细胞影响的关键调解者.
- 针对PI3K途径可能为与艾滋病毒相关的宫癌提供一种新的治疗策略.
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