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新型 miR-sc4 通过靶向 Cdk5r1 调控许旺细胞的增殖和迁移。

Novel miR-sc4 regulates the proliferation and migration of Schwann cells by targeting Cdk5r1.

机构信息

Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu, China.

出版信息

Mol Cell Biochem. 2018 Oct;447(1-2):209-215. doi: 10.1007/s11010-018-3305-0. Epub 2018 Jan 31.

DOI:10.1007/s11010-018-3305-0
PMID:29388152
Abstract

The proliferation and migration of Schwann cells are critical for the repair and regeneration of injured peripheral nerves. Noncoding RNAs, especially microRNAs (miRNAs), have been demonstrated to participate in regulating the biological behaviors of Schwann cells. Numerous differentially expressed novel miRNAs have been identified in the injured sciatic nerve stumps previously by Solexa sequencing. In the current research, we studied the biological function of a novel miRNA, miR-sc4, in detail. Outcomes from proliferation and migration assays suggested that miR-sc4 played an inhibitory role on the proliferation and migration of Schwann cells. Results from bioinformatic analysis, luciferase reporter assay, and rescue experiments suggested that miR-sc4 executed its effect through directly targeting cyclin-dependent kinase 5 activator 1 (Cdk5r1). Collectively, our current study revealed the biological functions of a novel miRNA, showed the effect of miR-sc4 in Schwann cell phenotypic changes, and thus indicated the involvement of miRNAs in peripheral nerve repair and regeneration.

摘要

施万细胞的增殖和迁移对于损伤外周神经的修复和再生至关重要。非编码 RNA,特别是 microRNAs(miRNAs),已被证明参与调节施万细胞的生物学行为。先前通过 Solexa 测序已在损伤的坐骨神经残端中鉴定出许多差异表达的新型 miRNA。在当前的研究中,我们详细研究了新型 miRNA miR-sc4 的生物学功能。增殖和迁移实验的结果表明,miR-sc4 对施万细胞的增殖和迁移起抑制作用。生物信息学分析、荧光素酶报告基因检测和挽救实验的结果表明,miR-sc4 通过直接靶向细胞周期蛋白依赖性激酶 5 激活物 1(Cdk5r1)发挥作用。综上所述,我们的研究揭示了新型 miRNA 的生物学功能,显示了 miR-sc4 在外周神经修复和再生中对施万细胞表型变化的影响,从而表明 miRNAs 参与了外周神经的修复和再生。

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本文引用的文献

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Schwann cell development, maturation and regeneration: a focus on classic and emerging intracellular signaling pathways.施万细胞的发育、成熟与再生:聚焦经典及新出现的细胞内信号通路
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Increased levels of miR-3099 induced by peripheral nerve injury promote Schwann cell proliferation and migration.外周神经损伤诱导的miR-3099水平升高促进雪旺细胞增殖和迁移。
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Int J Mol Sci. 2017 Jan 29;18(2):287. doi: 10.3390/ijms18020287.
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Int J Mol Sci. 2016 Dec 14;17(12):2101. doi: 10.3390/ijms17122101.
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Regulation of Schwann cell proliferation and migration by miR-1 targeting brain-derived neurotrophic factor after peripheral nerve injury.miR-1 靶向脑源性神经营养因子调控周围神经损伤后许旺细胞的增殖和迁移。
Sci Rep. 2016 Jul 6;6:29121. doi: 10.1038/srep29121.
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MiR-340 Regulates Fibrinolysis and Axon Regrowth Following Sciatic Nerve Injury.miR-340 调控坐骨神经损伤后的纤溶和轴突再生。
Mol Neurobiol. 2017 Aug;54(6):4379-4389. doi: 10.1007/s12035-016-9965-4. Epub 2016 Jun 25.
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miR-sc3, a Novel MicroRNA, Promotes Schwann Cell Proliferation and Migration by Targeting Astn1.miR-sc3,一种新型微小RNA,通过靶向Astn1促进雪旺细胞增殖和迁移。
Cell Transplant. 2016;25(5):973-82. doi: 10.3727/096368916X690520. Epub 2016 Jan 18.
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miR-sc8 Inhibits Schwann Cell Proliferation and Migration by Targeting Egfr.miR-sc8通过靶向Egfr抑制雪旺细胞增殖和迁移。
PLoS One. 2015 Dec 18;10(12):e0145185. doi: 10.1371/journal.pone.0145185. eCollection 2015.
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