N6-甲基氨酸修饰的circSMAD4 防止腰部不稳定性诱导的软骨端板骨化
Hanwen Li1, Yingchuang Tang1, Sihan Hu2
1Department of Orthopedic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215006, P. R. China.
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
|February 12, 2025
概括
稳定circSMAD4,一个圆形RNA,可以防止由腰部不稳定引起的软骨末板退化. 这个过程涉及m6A修饰和调节Yap1mRNA,为磁盘退化提供了潜在的治疗方法.
科学领域:
- 生物化学 生化学
- 分子生物学分子生物学
- 整形外科 整形外科 整形外科
背景情况:
- 腰椎不稳定导致软骨末板骨化和椎间盘退化.
- 在压力下,CircSMAD4,一个与Yap1相关的circRNA,是下调的.
研究的目的:
- 为了研究circSMAD4在维持异常压力下端板软骨恒温的作用.
- 阐明circSMAD4在预防软骨退化中的调节机制.
主要方法:
- 在实验室中,circSMAD4.4的淘汰和过度表达.
- 转录组测序和质谱学.
- 在体内进行AAV5介导的circSMAD4输送.
- 一个淘汰赛小鼠模型.
主要成果:
- circSMAD4敲击降解了Yap1mRNA;过度表达增强了Yap1表达和核转位.
- 由METTL14介导的m6A修饰稳定了circSMAD4的表达.
- circSMAD4通过m6A阅读器IGF2BP1调节Yap1mRNA,促进核转位和冠状细胞保护.
- circSMAD4过度表达拯救了LSI诱导的退化,但Yap1淘汰赛小鼠没有显示救援.
结论:
- 经m6A修饰的circSMAD4稳定了Yap1mRNA的表达和转位,防止在压力下软骨末板退化.
- circSMAD4代表了不稳定性诱导的椎间盘退化的一个潜在的治疗点.
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