LncRNA Neat1 mediates miR-124-induced activation of Wnt/β-catenin signaling in spinal cord neural progenitor cells

Stem Cell Research & Therapy

Yunlong Zou¹  Bin Yang²  Bai Xu²  Yanyun Yin²  Jianwu Dai²  Yannan Zhao²  Bing Chen²  Zhifeng Xiao²  Hongwei Song³  Yi Cui⁴  Xu Ma⁴ 

[1] EHBIO Gene Technology;Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences;Orthopaedics Surgery Department, China-Japan Union Hospital of Jilin University;Reproductive and Genetic Center of National Research Institute for Family Planning;

关键词: miR-124;    Neat1;    Spinal cord neural stem cells (SC-NPCs);    Spinal cord injury (SCI);   

DOI  :  10.1186/s13287-019-1487-3

来源: DOAJ

【 摘 要 】

Abstract Background Emerging evidence suggests that miR-124 performs important biological functions in neural stem cells (NSCs); it regulates NSC behavior and promotes the differentiation of NSCs into neurons, but the exact molecular mechanism remains unknown. And also, the role of miR-124 during spinal cord injury regeneration is unclear. Materials and methods In order to explore the function of miR-124 in neural differentiation, the molecular markers (Tuj1, Map2, and GFAP) correlated with the differentiation of NSCs were detected by immunofluorescence staining both in cultured mouse spinal cord progenitor cells (SC-NPCs) and in spinal cord injury (SCI) animal models. The migration ability and apoptosis of cultured SC-NPCs were also evaluated by Transwell migration assay and TUNEL assay. In addition, the relative expression of lnRNA Neat1- and Wnt/β-catenin signaling-related genes were detected by quantitative real-time PCR. Results In this study, we revealed that lncRNA Neat1 is involved in regulating Wnt/β-catenin signaling that is activated by miR-124 in SC-NPCs. LncRNA Neat1 was also found to play an important role in regulating neuronal differentiation, apoptosis, and migration of SC-NPCs. Furthermore, we demonstrated that overexpression of miR-124 resulted in elevated Neat1 expression, accompanied with the functional recovery of locomotion in a mouse model of spinal cord injury. Conclusions Our results confirm the therapeutic effectiveness of miR-124 on the functional recovery of injured spinal cord, supporting the rationale and feasibility of miR-124 for spinal cord injury treatment in future clinical therapy. Furthermore, we concluded that the miR-124-Neat1-Wnt/β-catenin signaling axis is involved in regulating the cell function of SC-NPCs, and this may offer novel therapeutic avenues for future treatment of SCI.

【 授权许可】

Unknown