激活CREB1促进人类乳头瘤病毒瘤基因表达和宫癌细胞转化
Yigen Li1,2, Molly R Patterson1,2, Ethan L Morgan3
1School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, West Yorkshire, UK.
Journal of medical virology
|August 11, 2023
概括
人类乳头瘤病毒 (HPV) 劫持CREB1,一种促进癌症的蛋白质,以推动宫癌的进展. 抑制CREB1会减少癌细胞的生长和迁移,从而揭示出一个关键的治疗点.
科学领域:
- 在瘤学瘤学.
- 病毒学 病毒学
- 分子生物学分子生物学
背景情况:
- 高风险的人类乳头瘤病毒 (HR-HPV) 通过表达E6和E7上蛋白质引起癌症.
- CREB1充当原瘤基因,其失调与各种癌症有关.
- 在宫癌中,HPV和CREB1之间的相互作用在很大程度上仍未被探索.
研究的目的:
- 为了研究CREB1在HPV驱动的宫癌中的作用.
- 阐明HPVcoproteins与CREB1活动之间的相互作用.
- 探索CREB1作为HPV+宫癌的潜在治疗标.
主要方法:
- 评估了感染HPV的角质细胞中的CREB1激活和宫病的进展.
- 在HPV+宫癌细胞系中利用了CREB1耗尽和活动抑制.
- 通过miR-203a和MAPK/MSK途径研究了CREB1的调节.
- 分析了CREB1与HPV促进体结合以及E6/E7瘤基因转录.
主要成果:
- 在生产性HPV感染中,CREB1被激活,其表达/酸化与宫疾病进展相关.
- 减少CREB1的消耗/抑制减少了增殖,上皮细胞转变为介质细胞的转变标记物,以及HPV+宫癌细胞的迁移.
- CREB1直接上调HPV E6/E7瘤基因转录,形成一个积极的反循环.
结论:
- 通过促进增殖和迁移,CREB1在HPV+宫癌中表现出致癌功能.
- 在HPVcoproteins激活CREB1的地方存在一个反循环,这反过来又增强了病毒瘤基因表达.
- 向CREB1为与HPV相关的宫癌提供了一个有前途的治疗策略.
关键词:
在CREB1中,CREB1是指CREB1,CREB1是指CREB1,CREB1是指CREB1.E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7在HPV中,HPV是HPV.宫癌:子宫癌是一种癌症.在 miR-203a 中,
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