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在DICER1癌症倾向中非细胞自主瘤促进
Randolph K Larsen1, Jason A Hanna2, Hongjian Jin3
1St. Jude Graduate School of Biomedical Sciences, Memphis, TN, USA.
Developmental cell
|September 30, 2025
概括
生殖系DICER1突变通过改变中性粒细胞的功能和增加中性粒细胞外细胞陷 (NETs) 来促进瘤生长. 向中性粒细胞或NET可能会降低具有DICER1突变的个体的癌症风险.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
背景情况:
- 与DICER1相关的瘤是由生殖系DICER1功能丧失突变 (DICER1+/-) 和体质第二次命中引起的.
- 生殖系DICER1+/-突变在启动瘤发生过程中的作用尚不清楚.
研究的目的:
- 调查生殖系DICER1哈普洛缺陷在促进瘤形成中的作用.
- 探索中性粒细胞和中性粒细胞外细胞陷 (NETs) 在与DICER1相关的瘤发生中的参与.
主要方法:
- 使用自发和异种移植的鼠标模型,以生殖线和条件的Dicer1异性删除的拉布多米索尔科马.
- 对中性粒细胞透的瘤组成进行了分析,并测量了循环的NETs.
- 采用遗传和药理策略来抑制NET释放.
主要成果:
- 精子线Dicer1的删除加速了瘤的发展,并增加了透率,与瘤细胞的条件删除不同.
- DICER1+/- 瘤显示中性粒细胞的丰富,并且携带瘤的小鼠表现出增加的NETs.
- 在DICER1+/-小鼠中,抑制NET释放显著降低了瘤的推广.
结论:
- 生殖系DICER1的哈普隆缺陷通过涉及中性粒细胞的非细胞自主机制促进了狂宫肌肉瘤的发展.
- 中性粒细胞和NET在DICER1+/-环境中促进瘤生长起着至关重要的作用.
- 向中性粒细胞或NETs是一个潜在的治疗策略,以减轻患有生殖系DICER1突变的个体的癌症风险.
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