转录因子 FoxM1 激活的 microRNA-335-3p 通过抑制 Fmr1 来抑制 p53 信号通路，从而维持神经干细胞的自我更新。
Transcriptional factor FoxM1-activated microRNA-335-3p maintains the self-renewal of neural stem cells by inhibiting p53 signaling pathway via Fmr1.
机构信息
Department of Neurosurgery, The Second Xiangya Hospital of Central South University, No. 139, Renmin Middle Road, Furong District, Changsha, 410011, Hunan Province, People's Republic of China.
出版信息
Stem Cell Res Ther. 2021 Mar 10;12(1):169. doi: 10.1186/s13287-021-02191-2.
BACKGROUND
New mechanistic insights into the self-renewal ability and multipotent properties of neural stem cells (NSCs) are currently under active investigation for potential use in the treatment of neurological diseases. In this study, NSCs were isolated from the forebrain of fetal rats and cultured to induce NSC differentiation, which was associated with low expression of the non-coding RNA microRNA-335-3p (miR-335-3p).
METHODS
Loss- and gain-of-function experiments were performed in NSCs after induction of differentiation.
RESULTS
Overexpression of miR-335-3p or FoxM1 and inhibition of the Fmr1 or p53 signaling pathways facilitated neurosphere formation, enhanced proliferation and cell cycle entry of NSCs, but restricted NSC differentiation. Mechanistically, FoxM1 positively regulated miR-335-3p by binding to its promoter region, while miR-335-3p targeted and negatively regulated Fmr1. Additionally, the promotive effect of miR-335-3p on NSC self-renewal occurred via p53 signaling pathway inactivation.
CONCLUSION
Taken together, miR-335-3p activated by FoxM1 could suppress NSC differentiation and promote NSC self-renewal by inactivating the p53 signaling pathway via Fmr1.
背景
目前，人们正在积极研究神经干细胞（NSCs）自我更新能力和多能性的新机制见解，以期将其用于治疗神经退行性疾病。在这项研究中，我们从胎鼠前脑中分离出 NSCs 并进行培养，以诱导 NSCs 分化，这与非编码 RNA 微 RNA-335-3p（miR-335-3p）的低表达有关。
方法
在 NSCs 分化诱导后进行了 miR-335-3p 的表达下调和过表达实验以及 FoxM1、Fmr1 和 p53 信号通路的抑制实验。
结果
过表达 miR-335-3p 或 FoxM1 并抑制 Fmr1 或 p53 信号通路可促进神经球的形成，增强 NSCs 的增殖和细胞周期进入，但限制 NSCs 的分化。机制上，FoxM1 通过结合其启动子区域正向调节 miR-335-3p，而 miR-335-3p 则靶向并负调控 Fmr1。此外，miR-335-3p 通过失活 p53 信号通路促进 NSC 自我更新。
结论
总之，FoxM1 激活的 miR-335-3p 通过 Fmr1 抑制 NSCs 的分化，并通过失活 p53 信号通路促进 NSCs 的自我更新。
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