CRISP3-PSP94复合体通过CITED2调节前列腺癌细胞和巨细胞中P2RX7介导的信号传递
Vaidehi Miya1, Bhakti R Pathak1
1Division of Cellular and Structural Biology, ICMR-National Institute for Research in Reproductive and Child Health, Parel, Mumbai, India.
概括
富含氨酸的分泌蛋白3 (CRISP3) 调节P2RX7水平,影响前列腺癌.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
背景情况:
- 富含氨酸的分泌蛋白3 (CRISP3) 和94个氨基酸的前列腺分泌蛋白 (PSP94) 在前列腺癌中具有逆表达,并且与预后不佳有关.
- 它们在瘤免疫微环境中的作用在很大程度上没有得到研究.
- 之前的研究发现了P2RX7,一种ATP-gated离子通道,在CRISP3敲击时被上调.
研究的目的:
- 在前列腺癌的背景下,研究CRISP3,PSP94和P2RX7之间的功能关系.
- 阐明P2RX7.7在CRISP3中介调节的基础上的分子机制.
- 探索CRISP3-PSP94复合体对P2RX7相关细胞过程的影响.
主要方法:
- 研究了复合人类CRISP3 (rhCRISP3) 和其与PSP94复合物的对PC3细胞和THP1巨细胞P2RX7表达的影响.
- 评估了ATP诱导的细胞毒性和IL-1β分泌.
- 利用抗体阵列来识别下游介质和CUT&RUN测试来确认P2RX7促进体中的蛋白质-DNA相互作用.
主要成果:
- 外源的rhCRISP3降低了P2RX7水平,减少了ATP诱导的细胞毒性和IL-1β分泌.
- 将CRISP3与PSP94复合取消了这些效应,并影响了CRISP3内细胞和flotillin-2相互作用.
- 富含氨酸的分泌蛋白3 (CRISP3) 通过CITED2调节了P2RX7的下调,这是一个转录的核心调节器,它降低了P2RX7促进者的p300水平.
结论:
- 在前列腺癌中揭示了将CRISP3,PSP94,P2RX7和CITED2联系在一起的新机制.
- CRISP3和PSP94相互作用调节P2RX7和CITED2水平,可能影响瘤免疫微环境.
- 研究结果表明,针对前列腺瘤中的CRISP3-PSP94-P2RX7轴具有治疗意义.
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