SRSF4-关联的ca-circFOXP1通过与宿主基因形成R循环来调节低氧诱导的PASMC扩散
Xinyue Song1,2, Ya Xu1,2, Mengnan Li1,2
1College of Pharmacy (X.S., Y.X., M.L., X.G., H.L., H.S., C.M., L.Z., X. Zhao, D.Z.), Harbin Medical University, P.R. China.
Arteriosclerosis, thrombosis, and vascular biology
|February 20, 2025
概括
与染色体相关的circFOXP1通过增加肺动脉光滑肌细胞增殖来促进肺高血压. 剪接因子SRSF4和m6A的修饰调节了这一过程,为疾病机制提供了洞察力.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 遗传学 是一个遗传学.
背景情况:
- 肺高血压 (PH) 是一种致命的疾病,其特点是肺动脉光滑肌肉细胞 (PASMC) 增殖和血管重塑.
- 已知与染色体相关的循环RNAs (circRNAs) 调节生物过程,但它们在PH中的作用尚不清楚.
研究的目的:
- 在PH的背景下,研究PASMC增殖中染色质相关circFOXP1 (ca-circFOXP1) 的功能和机制.
主要方法:
- 在低氧小鼠PASMC和Sugen5416+低氧 (SuHX) 小鼠模型中使用敲击技术研究ca-circFOXP1.
- 采用了生物信息分析,通过RNA净化分离染色质,细胞计数套件8,5-乙-2-脱氧氨和西方斑点测试.
主要成果:
- 在SuHX小鼠和缺氧PASMC中,ca-circFOXP1的表达显著升高.
- ca-circFOXP1通过R循环形成来调节宿主蛋白FOXP1水平,影响SMAD2酸化和PASMC增殖.
- m6A修饰促进ca-circFOXP1/FOXP1 R循环的形成,而拼接因子SRSF4提高ca-circFOXP1的表达.
结论:
- SRSF4上调ca-circFOXP1,m6A甲基化促进R循环形成,调节FOXP1和SMAD2酸化以调节PASMC增殖和肺血管重塑.
- 这些发现为了解缺氧PH病原和潜在的治疗见解提供了理论基础.
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