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损伤后坐骨神经近、远段差异表达的环状 RNA。

Differential expression of circular RNAs in the proximal and distal segments of the sciatic nerve after injury.

机构信息

Peripheral Neuropathy Research Center, Department of Molecular Neuroscience, College of Medicine, Dong-A University, Busan, South Korea.

出版信息

Neuroreport. 2020 Jan 8;31(1):76-84. doi: 10.1097/WNR.0000000000001371.

DOI:10.1097/WNR.0000000000001371
PMID:31764243
Abstract

To investigate the functions of circular RNAs (circRNAs) in axonal regeneration and degeneration after injury, circRNA expression profiles in the injured peripheral nerves were determined using a circRNA-based microarray. The results showed that 281 upregulated and 261 downregulated circRNAs were found in the proximal stump of the sciatic nerve after injury. In the distal stump after injury, 217 circRNAs were upregulated and 224 circRNAs were downregulated. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment and gene ontology (GO) analysis of circRNAs after injury were associated with axon regeneration pathways, including thyroid hormone, Ras signaling, endocytosis, and the ErbB signaling pathway, as well as with Schwann cell differentiation and proliferation, including the axon guidance, focal adhesion, Glutamatergic synapse, and MAPK signaling pathway. To verify the microarray results, among the regulated circRNAs, the upregulation of circRNA 012142 in both proximal and distal segments was validated using quantitative PCR analysis. The biological function of the circRNA 012412/microRNA/mRNA network based on GO analysis and KEGG pathway was identified in cell differentiation, phosphorylation, intracellular signaling transduction, and focal adhesion, the Rap1 signaling pathway. Thus, circRNAs after nerve injury may be involved in these biological functions during nerve regeneration and degeneration.

摘要

为了研究环状 RNA(circRNAs)在损伤后轴突再生和变性中的功能,使用基于 circRNA 的微阵列确定了损伤周围神经中的 circRNA 表达谱。结果表明,损伤后坐骨神经近端残端中发现 281 个上调和 261 个下调的 circRNAs。在损伤后的远端残端中,有 217 个 circRNAs 上调,224 个 circRNAs 下调。损伤后 circRNAs 的京都基因与基因组百科全书(KEGG)富集和基因本体论(GO)分析与轴突再生途径有关,包括甲状腺激素、Ras 信号转导、内吞作用和 ErbB 信号通路,以及施万细胞分化和增殖,包括轴突导向、焦点粘连、谷氨酸能突触和 MAPK 信号通路。为了验证微阵列结果,在受调控的 circRNAs 中,使用定量 PCR 分析验证了 circRNA 012142 在近端和远端段中的上调。基于 GO 分析和 KEGG 通路的 circRNA 012412/miRNA/mRNA 网络的生物学功能在细胞分化、磷酸化、细胞内信号转导和焦点粘连、Rap1 信号通路中得到了鉴定。因此,神经损伤后的 circRNAs 可能参与了神经再生和变性过程中的这些生物学功能。

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