MicroRNA124 Regulated Neurite Elongation by Targeting OSBP
MicroRNA124 Regulated Neurite Elongation by Targeting OSBP
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DOI：
10.1007/s12035-015-9540-4
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发表时间：
2016-11-01
影响因子：
5.1
通讯作者：
Wang, Xuemin
中科院分区：
文献类型：
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作者：
Gu, Xi;Li, Aili;Wang, Xuemin
MicroRNA-124(miR-124)是一种大脑特异的miRNA分子，在神经元分化过程中参与刺激轴突的生长和延长。然而，miR-124诱导轴突生长的直接靶基因和机制尚不清楚。在这项研究中，我们证明miR-124直接靶向并下调内源性氧固醇结合蛋白(OSBP)的表达。先前的一项研究发现，在大脑发育过程中，miR-124的表达增加。在本研究中，我们发现在C57BL/6小鼠大脑皮质发育过程中，OSBP的表达下降，这与miR-124的表达呈负相关。使用特定shRNAs敲除OSBP可促进Neuro-2a细胞和原代培养的小鼠皮质神经元的轴突生长和伸长。相反，OSBP的过表达强烈抑制了miR-124对Neuro-2a细胞轴突延长的促进作用。我们的结果提示，OSBP可能是miR-124调控轴突生长和伸长的靶点和下游效应因子。
MicroRNA-124 (miR-124), a brain-specific miRNA molecule, has been implicated in stimulating neurite outgrowth and elongation during neuronal differentiation. However, the direct target genes and the mechanisms of miR-124-induced neurite outgrowth are poorly understood. In this study, we demonstrated that miR-124 directly targeted and downregulated the endogenous expression of oxysterol-binding protein (OSBP). A previous study found that the expression of miR-124 increased during brain development. In the present study, we demonstrated that the expression of OSBP decreased during the development of the C57BL/6 mouse cortex, which was negatively correlated with miR-124 expression. OSBP knockdown using specific shRNAs promoted neurite outgrowth and elongation in both Neuro-2a cells and primary cultured mouse cortical neurons. Conversely, OSBP overexpression strongly repressed the neurite elongation-enhancing effect of miR-124 in Neuro-2a cells. Our results suggested that OSBP may be a target and downstream effector of miR-124 for regulating neurite outgrowth and elongation.