核促炎细胞因子S100A9通过转录因子TEAD1增强人乳头瘤病毒基因的表达
Seiichiro Mori1, Yoshiyuki Ishii1, Takamasa Takeuchi1
1Pathogen Genomics Center, National Institute of Infectious Diseases , Tokyo, Japan.
Journal of virology
|August 14, 2023
概括
核S100A9作为转录协活性剂,增强人类乳头瘤病毒 (HPV) 原基因表达. 这一发现将炎症与宫癌的进展联系起来,通过确定S100A9作为HPV致癌的关键参与者.
科学领域:
- 分子生物学分子生物学
- 在瘤学瘤学.
- 病毒学 病毒学
背景情况:
- 人类乳头瘤病毒 (HPV) 感染是导致子宫癌的主要原因.
- HPV 瘤基因 E6 和 E7 在宫癌发生过程中至关重要.
- 炎症在HPV驱动癌症中的作用尚未完全理解.
研究的目的:
- 确定调节HPV瘤基因表达的转录辅因子.
- 研究S100A9在HPV16长控制区域 (LCR) 调节中的作用.
- 阐明炎症与HPV瘤基因激活之间的联系.
主要方法:
- 在实验室中,从宫癌细胞中提取核蛋白的DNA-pulldown净化.
- 蛋白质组分析以确定与HPV16 LCR结合的TEAD1相关的辅因子.
- S100A9 敲击和强制核表达研究.
- 评估HPV瘤基因表达,细胞生长和对西斯的敏感性.
主要成果:
- 一种促炎细胞因子S100A9被确定为通过TEAD1.1与HPV16LCR结合的核蛋白.
- 核S100A9水平和LCR与炎症刺激的相关性增加.
- S100A9 Knockdown 降低了HPV瘤基因表达,宫癌细胞生长和对西斯普拉丁的抗性.
- 强迫核S100A9表达显示了相反的效果.
结论:
- 核S100A9作为转录协激活剂,通过TEAD1.1增强HPV瘤基因表达.
- 在宫癌中,S100A9将炎症反应与增加的HPV瘤基因活性联系在一起.
- 这些发现为HPV癌症发生中的炎症作用提供了新的分子洞察力.
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