三维染色体分析显示,Sp1作为一个调解者来编程和重编程HPV宿主在宫癌中的表观遗传结构
Canhui Cao1, Qian Xu2, Zhixian Zhu2
1Department of Gynecologic Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; National Clinical Research Center for Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Cancer letters
|March 12, 2024
概括
转录因子Sp1重新编程人乳头瘤病毒 (HPV) 宿主相互作用和表观遗传修饰. 抑制Sp1可能为HPV相关癌症提供新的治疗策略,并增强免疫疗法.
科学领域:
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 癌症生物学 癌症生物学
- 病毒学 病毒学
背景情况:
- 人类乳头瘤病毒 (HPV) 与癌症有关,但推动这一过程的表观遗传机制尚未完全理解.
- 了解HPV宿主染色体相互作用对于开发向疗法至关重要.
研究的目的:
- 通过使用高通量染色体构造捕获 (Hi-C) 来全面绘制HPV16/18宿主染色体相互作用.
- 研究转录因子Sp1在调解和重编程这些相互作用中的作用.
- 评估SP1抑制在HPV相关癌症和免疫治疗中的治疗潜力.
主要方法:
- 高通量染色体构造捕获 (Hi-C) 来映射染色体相互作用.
- 准Sp1观察对基因组修饰和瘤基因表达的影响.
- 在体内研究中使用人性化的患者衍生异种移植 (PDX-HuHSC-NSG) 模型.
- 单细胞转录组分析以确定子宫癌细胞中的Sp1丰富.
主要成果:
- 鉴定出Sp1是HPV与宿主染色体相互作用的关键媒介.
- Sp1抑制重新编程了活跃的基因素修饰和HPV与宿主相互作用,降低了瘤基因的调节 (KLF5/MYC).
- 在宫癌模型中,Sp1抑制上调了免疫检查点基因,并促进了抗PD-1免疫疗法.
- 发现Sp1在宫癌的上皮细胞中富含.
结论:
- 在编程和重编程HPV宿主表观遗传结构中,Sp1起着关键作用.
- 准Sp1,可能是用plicamycin,为HPV相关癌症提供了一个有前途的治疗策略.
- 通过调节瘤免疫微环境,Sp1抑制可以增强抗PD-1免疫疗法.
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