Long Non-coding RNA Maternally Expressed 3 Increases the Expression of Neuron-Specific Genes by Targeting miR-128-3p in All-Trans Retinoic Acid-Induced Neurogenic Differentiation From Amniotic Epithelial Cells
Long Non-coding RNA Maternally Expressed 3 Increases the Expression of Neuron-Specific Genes by Targeting miR-128-3p in All-Trans Retinoic Acid-Induced Neurogenic Differentiation From Amniotic Epithelial Cells
复制标题
母体表达的长非编码 RNA 3 通过靶向 miR-128-3p 在全反式视黄酸诱导的羊膜上皮细胞神经原性分化中增加神经元特异性基因的表达
DOI：
10.3389/fcell.2019.00342
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发表时间：
2019-12-23
影响因子：
5.5
通讯作者：
Bai, Chunyu
中科院分区：
文献类型：
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作者：
Gao, Yuhua;Zhang, Ranxi;Bai, Chunyu
MicroRNA (miR)-128-3p是一种脑富集miRNA，参与神经细胞分化调控和神经元保护，但miR-128-3p调控其靶基因和下游基因影响成体干细胞细胞命运的机制尚不清楚。在这项研究中，我们发现miR-128-3p在全反式维甲酸（ATRA）诱导的羊膜上皮细胞（AECs）神经源性分化过程中下调。我们研究了miR-128-3p在Notch通路和被预测参与miR-128-3p信号传导的神经元特异性基因表达中的作用，以阐明其在下游神经源性分化的遗传调控中的作用。我们的研究结果表明，miR-128-3p是神经元特异性基因β iii -微管蛋白、神经元特异性烯醇酶（NSE）和多唾液酸-神经细胞粘附分子（PSA-NCAM）转录的负调节因子，通过靶向Jagged 1抑制Notch信号通路的激活。我们还使用生物信息学算法筛选miR-128-3p与长链非编码RNA （lnc）和环状RNA作为竞争内源性RNA的相互作用，以进一步阐明潜在的下调分子机制。母体表达3的lncRNA通过ATRA/cAMP/CREB通路上调，而它又被miR-128-3p直接下调，从而增加神经元的分化量。因此，内源性mirna参与了aec的神经源性分化，在开发有效的细胞移植治疗神经退行性疾病的过程中应予以考虑。
MicroRNA (miR)-128-3p is a brain-enriched miRNA that participates in the regulation of neural cell differentiation and the protection of neurons, but the mechanisms by which miR-128-3p regulates its target and downstream genes to influence cell fate from adult stem cells are poorly understood. In this study, we show down-regulation of miR-128-3p during all-trans retinoic acid (ATRA)-induced neurogenic differentiation from amniotic epithelial cells (AECs). We investigated miR-128-3p in both the Notch pathway and in the expression of neuron-specific genes predicted to be involved in miR-128-3p signaling to elucidate its role in the genetic regulation of downstream neurogenic differentiation. Our results demonstrate that miR-128-3p is a negative regulator for the transcription of the neuron-specific genes beta III-tubulin, neuron-specific enolase (NSE), and polysialic acid-neural cell adhesion molecule (PSA-NCAM) via targeting Jagged 1 to inhibit activation of the Notch signaling pathway. We also used bioinformatics algorithms to screen for miR-128-3p interactions with long non-coding (lnc) RNA and circular RNA as competing endogenous RNAs to further elucidate underlying down-regulated molecular mechanisms. The lncRNA maternally expressed 3 is up-regulated by the ATRA/cAMP/CREB pathway, and it, in turn, is directly down-regulated by miR-128-3p to increase the amount of neuron differentiation. Endogenous miRNAs are, therefore, involved in neurogenic differentiation from AECs and should be considered during the development of effective cell transplant therapies for the treatment of neurodegenerative disease.