升级的YTHDC1调解热囊细胞功能障碍,通过增强的RPL37翻译,在ART怀孕中诱导早产
Wei Li1,2, Qianqian Zhang1,2, Meng Ni1,2
1The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, 910# Hengshan Road, Shanghai, China.
Cellular and molecular life sciences : CMLS
|December 26, 2024
概括
辅助生殖技术 (ART) 增加了早产风险. 雌激醇通过RXRA对YTHDC1进行上调,促进热囊细胞功能和早产. 针对YTHDC1提供了一个潜在的治疗策略.
科学领域:
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 生殖生物学 生殖生物学
- 疾病的分子机制.
背景情况:
- 辅助生殖技术 (ART) 怀孕的早产率更高.
- 与ART相关的早产的分子基础,特别是涉及RNA m6A修饰的分子基础,尚不清楚.
- 一个m6A阅读器YTHDC1在早产中起着未明确的作用.
研究的目的:
- 研究YTHDC1在ART相关的早产中的作用和表观遗传机制.
- 阐明YTHDC1如何影响热囊细胞功能,并有助于早产.
- 确定潜在的治疗点,以预防与ART相关的早产.
主要方法:
- 在 trofhoblast 细胞中过度表达和击倒 YTHDC1.
- CCK-8,EdU,Transwell和流式细胞计测试用于评估热囊细胞功能.
- 通过RNA-seq,RIP-seq,MeRIP-seq,ChIP-seq和露西法酶记者测试来探索分子通路.
- 人类和小鼠早产胎盘模型中的雌激素 (E2) 暴露.
- 在体内给予向YTHDC1的siRNA.
主要成果:
- 人类和小鼠ART孕育的早产胎盘中YTHDC1的升高.
- 过度表达YTHDC1促进了热囊细胞的增殖和迁移,同时抑制了亡.
- 雌激醇通过在热囊细胞中的RXRA对YTHDC1进行上调.
- YTHDC1以一种m6A依赖的方式增强了RPL37的翻译.
- 针对YTHDC1的siRNA延迟了早产的进展.
结论:
- E2/RXRA/YTHDC1/RPL37轴是关键的表观遗传途径在ART相关的早产.
- YTHDC1在调节热囊细胞功能和促进早产方面发挥着至关重要的作用.
- YTHDC1代表了一个潜在的预后生物标志物和早产治疗标.
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