由HOXA4激活的IncRNAHOTAIRM1通过与蛋白质合作伙伴HSPA5的直接相互作用驱动HUVEC的扩散
Yu Zhou1,2, Qiang Wu3, Xiangshu Long2
1Medical College, Guizhou University, Guiyang, 550025, Guizhou, China.
Inflammation
|October 29, 2023
概括
长非编码RNAHOTAIRM1在动脉样硬化中受到上调,并影响内皮细胞增殖和亡. 这项研究揭示了一个涉及HOXA4,HOTAIRM1和HSPA5的调节电路,为心血管疾病提供了潜在的治疗点.
科学领域:
- 分子心脏病学分子心脏病学
- 在RNA生物学,RNA生物学.
- 动脉样硬化病原体的产生
背景情况:
- 动脉样硬化 (AS) 仍然是心血管死亡的主要原因,尽管了解其病变的进展.
- 长非编码RNAs (lncRNAs) 越来越多地被认为是AS发展的关键调节者.
- 在人静脉内皮细胞 (HUVEC) 和AS中HOTAIRM1的特定作用仍然在很大程度上未被探索.
研究的目的:
- 在动脉样硬化条件下研究HUVEC中lncRNAHOTAIRM1的功能和机制.
- 在内皮细胞生物学中阐明涉及HOTAIRM1,HOXA4和HSPA5的调控网络.
- 为了确定AS治疗的潜在分子标.
主要方法:
- 定量实时PCR评估HOTAIRM1表达在HUVECs刺激与氧化低密度脂蛋白 (ox-LDL).
- 功能性测试包括细胞增殖和细胞亡测试后HOTAIRM1敲击.
- 染色体免疫沉 (ChIP) 测试以确定HOXA4与HOTAIRM1促进体的结合.
- RNA免疫沉 (RIP) 试验用于研究HOTAIRM1和HSPA5.5之间的相互作用.
主要成果:
- 在ox-LDL刺激后,HOTAIRM1表达在HUVEC中显著上调,这表明它参与AS.
- 在存在或缺乏ox-LDL的情况下,HOTAIRM1 knockdown抑制了HUVEC的增殖,并促进了亡.
- HOXA4直接激活HOTAIRM1转录,形成一个积极的反循环,HOTAIRM1以转录依赖的方式与HSPA5相互作用.
- HSPA5过度表达部分挽救了HOTAIRM1枯竭对HUVEC增殖的抑制作用.
结论:
- 该研究确定了一种新型的监管轴,包括HOXA4,HOTAIRM1和HSPA5,可以调节HUVEC的扩散.
- HOTAIRM1在有关动脉样硬化的内皮细胞功能中发挥着关键作用.
- HOXA4-HOTAIRM1-HSPA5通路代表了开发针对动脉样硬化的新型治疗策略的有希望的目标.
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