MYC通过microRNA 17/20a调节CSF1表达,以调节骨髓瘤中与瘤相关的巨细胞
Bikesh K Nirala1, Tajhal D Patel1, Lyazat Kurenbekova1
1Texas Children's Cancer and Hematology Centers and The Faris D. Virani Ewing Sarcoma Center.
JCI insight
|June 6, 2023
概括
在骨髓瘤 (OS) 中的c-MYC放大驱动了瘤的快速生长和转移. 这种瘤基因改变了瘤的微环境,通过降低关键因素来消耗像巨细胞这样的免疫细胞.
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:
- 骨髓瘤 (OS) 是一个常见的儿科骨癌.
- 染色体8q24的放大,包括c-MYC瘤基因,发生在20-30%的OS病例中,与预后不佳有关.
- 在OS中调节瘤微环境 (TME) 中c-MYC的作用尚未完全理解.
研究的目的:
- 研究c-MYC如何影响OS瘤及其TME的机制.
- 描述一种新的基因工程小鼠模型 (GEMM),用于研究c-MYC驱动的OS.
- 在OS中识别受c-MYC调节的分子通路.
主要方法:
- 一个骨质细胞特异性c-MycT58A p53fl/+ knockin GEMM的生成和分子特征.
- 对MYC依赖基因表达特征的分析.
- 评估TME内的免疫细胞种群.
- 在体外和体内验证使用细胞系和降解标记-MYC模型系统.
主要成果:
- Myc-knockin GEMM 呈现出快速瘤发育和高转移发病率.
- 鼠标模型中的MYC依赖基因特征反映了人类过度激活的MYC操作系统.
- 过度激活的c-MYC导致免疫衰竭的TME,其特征是白细胞减少,特别是巨细胞.
- 通过增加microRNA 17/20a表达,c-MYC过度激活降低了巨细胞殖民地刺激因子1的调节,减少了巨细胞群.
结论:
- 过度激活的c-MYC促进了侵略性的OS表型,包括快速生长和转移.
- c-MYC通过产生免疫力低下的TME,显著影响OS免疫格局.
- 一种涉及微RNA 17/20a和巨细胞殖民地刺激因子1的新机制调解了c-MYC对OS巨细胞招募的影响.
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