Department of Regenerative Medicine, Tongji University School of Medicine, 1239 Siping Road, Shanghai 200092, P.R. China.
Curr Mol Med. 2013 Nov;13(9):1432-45. doi: 10.2174/15665240113139990072.
MicroRNAs (miRNAs) are a class of small non-encoding RNAs that regulate gene expression at the posttranscriptional level. MiRNAs may characterize not only specific stages of the development of the neural cell population in CNS, but also distinct types of neural cells. However, the common pathways of the neural enriched miRNAs involved in neurogenesis of specific cell lineages remain poorly understood. In this report, in order to get insights into the common role of the miRNAs shared by cerebellum and forebrain, we studied the regulatory mechanism of neural enriched-miRNA in neural progenitor cell (NPCs) differentiation. Here, we identified a new cerebellum-enriched rno-miR-592 in rat cerebellum. It showed that rno-miR-592 was a neural enriched miRNA and may play an important role in rat embryonic neurogenesis or/and astrogliogenesis. We used both gain-of -function and loss-of -function approaches to demonstrate that rno-miR-592 could change the balance between neuron- and astrocyte- like differentiation and neuronal morphology. We observed that miR-592 could induce astrogliogenesis differentiation arrest or/and enhance neurogenesis in vitro. Meanwhile, silencing of miR-592 was not beneficial for neuronal maturation. We also identified Lrrc4c and Nfasc as miR-592 target genes, and miR-592 could affect the changes of Lrrc4c and Nfasc expression levels, suggesting that these two target genes may be involved in miR-592 regulative function in NPCs differentiation and neuronal maturation. Thus, we conclude that rno-miR-592 may affect the neural lineage differentiation via reducing astrogliogenesis or/and enhancing neurogenesis at least in part through regulating its target genes Lrrc4c and Nfasc in vitro. Together, we report here for the first time the important role of miR-592 in rat NPCs differentiation and neuronal maturation.
微小 RNA(miRNA)是一类小的非编码 RNA,可在转录后水平调节基因表达。miRNA 不仅可以表征中枢神经系统神经细胞群体发育的特定阶段,还可以表征不同类型的神经细胞。然而,参与特定细胞谱系神经发生的富含神经 miRNA 的常见途径仍知之甚少。在本报告中,为了深入了解小脑和前脑共有的 miRNA 的共同作用,我们研究了神经前体细胞(NPC)分化中富含神经 miRNA 的调控机制。在这里,我们在大鼠小脑鉴定到一种新的小脑富集 rno-miR-592。结果表明 rno-miR-592 是一种富含神经的 miRNA,可能在大鼠胚胎神经发生或/和星形胶质发生中发挥重要作用。我们使用增益功能和失活功能两种方法来证明 rno-miR-592 可以改变神经元样和星形胶质细胞样分化以及神经元形态之间的平衡。我们观察到 miR-592 可以诱导星形胶质细胞分化阻滞或/和增强体外神经发生。同时,miR-592 的沉默不利于神经元成熟。我们还鉴定出 Lrrc4c 和 Nfasc 是 miR-592 的靶基因,miR-592 可以影响 Lrrc4c 和 Nfasc 表达水平的变化,提示这两个靶基因可能参与 miR-592 调节 NPC 分化和神经元成熟的功能。因此,我们得出结论,rno-miR-592 可能通过降低星形胶质细胞发生或/和增强体外神经发生来影响神经谱系分化,至少部分通过调节其靶基因 Lrrc4c 和 Nfasc。总之,我们首次报道了 miR-592 在大鼠 NPC 分化和神经元成熟中的重要作用。