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外基因组RNA无屏蔽对 电流激活到癌症的模式识别受体信号
Barzin Y Nabet1, Yu Qiu1, Jacob E Shabason1
1Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Cell
|July 15, 2017
概括
乳腺癌细胞触发 stromal NOTCH-MYC,从而增加RNA RN7SL1. 通过激活模式识别受体 (PRRs) 在外体中促进炎症,瘤生长,转移和治疗抵抗.
科学领域:
- 分子生物学
- 癌症研究
- 免疫学
背景情况:
- 流体纤维细胞和癌细胞相互作用,影响癌症的进展和治疗耐药性.
- 内源RNA可以作为损伤相关的分子模式 (DAMPs) 来激活模式识别受体 (PRRs),但通常是屏蔽的.
- 由树皮细胞释放的非屏蔽RNA可以促进炎症和癌症的攻击性.
研究的目的:
- 在癌症进展和治疗耐药性方面研究结构RNA调节的作用.
- 识别特定的RNA分子和瘤细胞通信中的途径.
- 了解体激活如何导致炎症和瘤促进信号的释放.
主要方法:
- 研究了乳腺癌细胞触发的流体纤维细胞中的NOTCH-MYC信号.
- 分析了POL3在RNARN7SL1表达的作用.
- 研究了RN7SL1和RNA结合蛋白SRP9/14之间的相互作用.
- 研究了通过外体转移到免疫和癌细胞的未被屏蔽的RN7SL1.
- 评估了像RIG-I这样的模式识别受体 (PRR) 的激活.
- 使用患者瘤和血液样本进行了验证.
主要成果:
- 乳腺癌细胞触发 stromal NOTCH-MYC,导致RN7SL1的表达增加.
- 增加的 RN7SL1 改变了它与 SRP9/14 的结合,导致没有屏蔽的 RN7SL1.
- 不被屏蔽的RN7SL1在树突外体中释放并转移到其他细胞.
- 在免疫细胞中,未受保护的RN7SL1驱动着炎症反应.
- 在乳腺癌细胞中,非屏蔽的RN7SL1激活RIG- I,增强瘤生长,转移和治疗耐药性.
- 来自患者样本的证据支持RNA在侵袭性癌症特征中的作用.
结论:
- 调节RNA脱是一种关键的机制,它将基层激活与RNA DAMP的释放结合起来.
- 没有屏蔽的RN7SL1促进了侵袭性癌症表型,包括生长,转移和耐药性.
- 针对RNA脱屏路可能为乳腺癌提供新的治疗策略.
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