Up-regulation of miR-10a-5p expression inhibits the proliferation and differentiation of neural stem cells by targeting Chl1  

作　　者：Juan Zhang Lihong Yang Yuqing Sun Li Zhang Yufei Wang Ming Liu Xiujuan Li Yuxiang Liang Hong Zhao Zhizhen Liu Zhiyong Qiu Ting Zhang Jun Xie 

机构地区：[1]Department of Biochemistry and Molecular Biology,School of Basic Medical Science,Shanxi Key Laboratory of Birth Defect and Cell Regeneration,MOE Key Laboratory of Coal Environmental Pathogenicity and Prevention,Shanxi Medical University,Taiyuan 030001,China [2]Department of Cell Biology and Genetics,School of Basic Medical Science,Shanxi Medical University,Taiyuan 030001,China [3]Beijing Municipal Key Laboratory of Child Development and Nutriomics,Capital Institute of Pediatrics,Beijing 100020,China

出　　处：《Acta Biochimica et Biophysica Sinica》2024年第10期1483-1497,共15页生物化学与生物物理学报（英文版）

基　　金：supported by the grants from the National Natural Science Foundation of China(No.81671462);the Fund for Shanxi“1331 Project”Key Subjects Construction(No.1331KSC);the Natural Science Foundation of Shanxi Province(Nos.20210302124184 and 20210302124016);the Shanxi Province Key Laboratory of Birth Defects and Cell Regeneration and Research Project Supported by Shanxi Scholarship Council of China.

摘　　要：Neural tube defects(NTDs)are characterized by the failure of neural tube closure during embryogenesis and are considered the most common and severe central nervous system anomalies during early development.Recent microRNA(miRNA)expression profiling studies have revealed that the dysregulation of several miRNAs plays an important role in retinoic acid(RA)-induced NTDs.However,the molecular functions of these miRNAs in NTDs remain largely unidentified.Here,we show that miR-10a-5p is significantly upregulated in RA-induced NTDs and results in reduced cell growth due to cell cycle arrest and dysregulation of cell differentiation.Moreover,the cell adhesion molecule L1-like(Chl1)is identified as a direct target of miR-10a-5p in neural stem cells(NSCs)in vitro,and its expression is reduced in RA-induced NTDs.siRNA-mediated knockdown of intracellular Chl1 affects cell proliferation and differentiation similar to those of miR-10a-5p overexpression,which further leads to the inhibition of the expressions of downstream ERK1/2 MAPK signaling pathway proteins.These cellular responses are abrogated by either increased expression of the direct target of miR-10a-5p(Chl1)or an ERK agonist such as honokiol.Overall,our study demonstrates that miR-10a-5p plays a major role in the process of NSC growth and differentiation by directly targeting Chl1,which in turn induces the downregulation of the ERK1/2 cascade,suggesting that miR-10a-5p and Chl1 are critical for NTD formation in the development of embryos.

关 键 词：neural tube defects retinoic acid miR-10a-5p cell adhesion molecule L1-like(Chl1) ERK1/2 MAPK signaling pathway 

分 类 号：R329.2[医药卫生—人体解剖和组织胚胎学]