来自瘤的miR-6794-5p通过促进M2巨细胞极化来增强癌症生长
Jae Yeon Choi1,2, Hyun Jeong Seok1, Dong Hyeon Lee1
1Division of Radiation Biomedical Research, Korea Institute of Radiological & Medical Sciences, 75 Nowon-ro, Nowon-gu, Seoul, 01812, Republic of Korea.
Cell communication and signaling : CCS
|March 24, 2024
概括
来自瘤的miR-6794-5p通过将巨细胞重新编程到免疫抑制M2状态来促进癌症的攻击性,从而阻碍了抗瘤免疫力. 这项研究揭示了一种由癌细胞操纵瘤微环境的新机制.
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:
- 固体瘤操纵瘤微环境 (TME) 以促进恶性瘤和治疗耐药性.
- 了解TME中的细胞-细胞通信对于有效的癌症治疗至关重要.
- 在固体瘤中Bcl-w过度表达的作用及其与TME中免疫细胞的相互作用在很大程度上仍未被探索.
研究的目的:
- 为了确定由Bcl-w-过度表达瘤分泌的外体中的关键因素.
- 分析这些因素与TME的相互作用及其对瘤恶性病变的贡献.
- 阐明由瘤衍生因素影响免疫细胞的特定机制.
主要方法:
- 来自Bcl-w-过度表达癌细胞的外基因组使用miRNA数组进行了分析.
- 鉴定的miRNA,miR-6794-5p的功能通过过度表达研究,qRT-PCR,西部斑点和体外测试 (入侵,伤口愈合,球体形成) 来评估.
- 研究了作用机制,包括基因相互作用 (SOCS1) 和巨细胞两极分化 (共同培养,IHC,流细胞测量).
主要成果:
- 来自Bcl-w过度表达细胞的外基因组含有高水平的miR-6794-5p.
- 过度表达miR-6794-5p通过抑制瘤抑制剂SOCS1.1,增强了瘤细胞的迁移,入侵和干性.
- 来自瘤的miR-6794-5p通过JAK1/STAT3通路诱导了巨细胞的M2极化,导致IL-10分泌量增加和免疫抑制的TME. 动物模型证实了M2巨细胞的增加和M1巨细胞和CD8+T细胞的减少.
结论:
- MiR-6794-5p是瘤分泌的关键因子,可以改变TME.
- 来自瘤的miR-6794-5p通过巨细胞重编程诱导免疫抑制环境,促进瘤的攻击性.
- 向miR-6794-5p或其下游通路可能提供针对固体瘤的治疗策略.
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