Circ_0002331 与ELAVL1相互作用,通过调节CCND2mRNA稳定性来改善ox-LDL诱导的血管内皮细胞功能障碍
1Department of Cardiovascular Medicine, Lishui People's Hospital, Lishui, Zhejiang, China.
Cardiovascular toxicology
|May 14, 2024
概括
循环RNAcirc_0002331在动脉样硬化 (AS) 中是下调的. 恢复circ_0002331通过调节CCND2.2.保护人类脉内皮细胞 (HUVECs) 免受ox-LDL诱导的功能障碍.
科学领域:
- 分子生物学分子生物学
- 心血管研究研究心血管研究
背景情况:
- 循环RNAs (circRNAs) 是动脉样硬化 (AS) 的新兴调节者.
- 在AS中circ_0002331的特定作用和机制在很大程度上仍未被探索.
- 了解circRNA功能对于开发新型AS疗法至关重要.
研究的目的:
- 在AS.AS.的背景下研究circ_0002331的功能和机制.
- 阐明涉及内皮细胞中circ_0002331,CCND2和ELAVL1的调节途径.
- 评估circ_0002331对AS的治疗潜力.
主要方法:
- 通过使用ox-LDL处理的HUVECs建立了体外AS模型.
- 通过qRT-PCR量化了circ_0002331,CCND2和ELAVL1的表达.
- 通过各种测试评估细胞功能 (增殖,细胞亡,迁移,入侵,血管生成).
- 分析了蛋白质水平,RNA-蛋白相互作用 (RIP,RNA拉下),以及细胞局部化 (FISH).
主要成果:
- 在AS患者和ox-LDL治疗的HUVEC中,circ_0002331的表达显著下调.
- 过度表达circ_0002331逆转了ox-LDL诱导的HUVEC功能障碍,促进有益的功能并抑制有害的功能.
- 通过与ELAVL1.1相互作用,circ_0002331正调节了CCND2并增强了CCND2mRNA的稳定性.
- 证实了CCND2的作用,因为其过度表达模仿了保护作用,并且敲击逆转了circ_0002331的益处.
结论:
- circ_0002331 作为对AS的保护因素.
- 该机制涉及circ_0002331绑定ELAVL1以稳定CCND2mRNA,从而改善内皮细胞功能障碍.
- circ_0002331代表了AS治疗的有前途的治疗标.
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