O-GlcNAcylated YTHDF2通过通过m6A修改调节瘤抑制基因PER1促进膀癌的进展
Li Wang1,2,3, Da Ren4, Zeqiang Cai4
1Department of Thoracic Surgery, Second Xiangya Hospital, Central South University, Changsha 410011. li-wang@csu.edu.cn.
概括
通过降低瘤抑制剂PER1的调节,与YTHDF2的O相关的N-乙糖胺修饰促进了膀癌. 这种m6A介导的机制突出了膀癌的新治疗点.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 膀癌是一种常见的恶性瘤,预后不佳.
- N6-甲基氨酸 (m6A) 修饰,特别是YTHDF2蛋白,与膀癌的进展有关.
- 在膀癌中的YTHDF2功能中,O-链接的N-乙糖胺 (O-GlcNAc) 修饰的作用仍然不清楚.
研究的目的:
- 研究膀癌中YTHDF2的O-GlcNAc修饰的分子机制.
- 为了阐明YTHDF2如何调节其目标基因,周期昼夜调节器1 (PER1).
- 确定本条例对膀癌细胞增殖的影响.
主要方法:
- 在膀癌组织和细胞系中分析YTHDF2和PER1的表达,使用TCGA,RT-qPCR,西式涂抹和免疫组织化学.
- 功能测定包括CCK-8,殖民地形成和EDU,以评估YTHDF2操纵后的细胞增殖.
- 生物信息预测和免疫沉以检测YTHDF2 O-GlcNAc修饰和无处不在.
- MeRIP测试测量PER1 m6A的修饰,并评估mRNA的稳定性.
主要成果:
- 在膀癌组织和细胞中,YTHDF2及其O-GlcNAc修饰被显著上调.
- YTHDF2抑制了扩散和降低了主要的扩散标志物 (PCNA,MCM2,Cyclin D1).
- O-GlcNAc 修饰影响了 YTHDF2 蛋白质的稳定性; YTHDF2 针对 PER1 mRNA 通过 m6A 降解,而 PER1 敲击逆转了 YTHDF2 敲击诱导的增殖抑制.
结论:
- 对YTHDF2的O-GlcNAc修饰促进了膀癌的发展.
- 这种促进通过通过m6A介导的转录后调节下调瘤抑制基因PER1发生.
- 针对YTHDF2的O-GlcNAc修饰,为膀癌提供了一个潜在的治疗策略.
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