中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2022, Vol. 17 ›› Issue (2): 401-408.doi: 10.4103/1673-5374.317987

• 原著:神经损伤修复保护与再生 • 上一篇    下一篇

miR-103-3p靶向Ndel1可调节神经干细胞的增殖和分化

  

  • 出版日期:2022-02-15 发布日期:2021-10-08

miR-103-3p targets Ndel1 to regulate neural stem cell proliferation and differentiation

Wen Li1, 2, 3, #, Shan-Shan Wang1, 2, 3, #, Bo-Quan Shan1, 2, 3, Jian-Bing Qin1, 2, 3, He-Yan Zhao1, 2, 3, Mei-Ling Tian1, 2, 3, Hui He1, 2, 3, Xiang Cheng1, 2, 3, Xin-Hua Zhang1, 2, 3, *, Guo-Hua Jin1, 2, 3, *#br#   

  1. 1Department of Human Anatomy, Institute of Neurobiology, Nantong University, Nantong, Jiangsu Province, China; 2Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Nantong, Jiangsu Province, China; 3Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu Province, China
  • Online:2022-02-15 Published:2021-10-08
  • Contact: Guo-Hua Jin, PhD, jguohua@ntu.edu.cn; Xin-Hua Zhang, PhD, zhangxinhua@ntu.edu.cn.
  • Supported by:
    The study was supported by Graduate Scientific Research Innovation Program of Jiangsu Province of China, No. KYCX19 2066 (to WL); and Project Funded by the Priority Academic Program Development (PAPD) of Jiangsu Higher Education institutions China, No. 03081023 (to GHJ).

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摘要：

成年神经干细胞的调节对于神经发生至关重要。微小RNA是一种小型内源性RNA，可转录后调控基因表达并影响负责多个细胞过程的信号网络。（1）体外实验中将miR-103-3p模拟物转染到胚胎海马神经干细胞中，发现miR-103-3p可抑制神经干细胞的增殖和分化，同时促进细胞凋亡，且miR-103-3p可通过结合Ndel1的3'非翻译区负调控Ndel1的表达；（2）将过表达Ndel1的慢病毒转染到miR-103-3p过表达的神经干细胞后，其增殖和分化明显增加，而凋亡受到抑制，且Wnt/β-Catenin通路相关蛋白Wnt3a，β-catenin，磷酸化糖原合成酶激酶3β，LEF1，c-myc，c-Jun和细胞周期蛋白D1表达减少；（3）表明Ndel1是miR-103-3p的新靶点，且miR-103-3p可通过抑制神经干细胞的增殖，促进细胞凋亡和分化，并激活Wnt/β-Catenin通路而发挥作用。实验于2020年8月26日经南通大学动物伦理委员会批准（批准号20200826-003）。

https://orcid.org/0000-0003-2402-6769 (Wen Li); https://orcid.org/0000-0001-7853-2574 (Guo-Hua Jin)

关键词: miR-103-3p, Ndel1, 神经干细胞, 增殖, 凋亡, 分化, 经典的Wnt通路, 神经发生

Abstract: The regulation of adult neural stem cells (NSCs) is critical for lifelong neurogenesis. MicroRNAs (miRNAs) are a type of small, endogenous RNAs that regulate gene expression post-transcriptionally and influence signaling networks responsible for several cellular processes. In this study, miR-103-3p was transfected into neural stem cells derived from embryonic hippocampal neural stem cells. The results showed that miR-103-3p suppressed neural stem cell proliferation and differentiation, and promoted apoptosis. In addition, miR-103-3p negatively regulated NudE neurodevelopment protein 1-like 1 (Ndel1) expression by binding to the 3′ untranslated region of Ndel1. Transduction of neural stem cells with a lentiviral vector overexpressing Ndel1 significantly increased cell proliferation and differentiation, decreased neural stem cell apoptosis, and decreased protein expression levels of Wnt3a, β-catenin, phosphor-GSK-3β, LEF1, c-myc, c-Jun, and cyclin D1, all members of the Wnt/β-catenin signaling pathway. These findings suggest that Ndel1 is a novel miR-103-3p target and that miR-103-3p acts by suppressing neural stem cell proliferation and promoting apoptosis and differentiation. This study was approved by the Animal Ethics Committee of Nantong University, China (approval No. 20200826-003) on August 26, 2020.

Key words: apoptosis, canonical Wnt pathway, differentiation, MiR-103-3p, Ndel1, neural stem cells, neurogenesis, proliferation 

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