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大鼠坐骨神经损伤后背根神经节中长链非编码 RNA 表达的改变。

Altered long noncoding RNA expressions in dorsal root ganglion after rat sciatic nerve injury.

机构信息

Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong 226001, China.

出版信息

Neurosci Lett. 2013 Feb 8;534:117-22. doi: 10.1016/j.neulet.2012.12.014. Epub 2012 Dec 26.

DOI:10.1016/j.neulet.2012.12.014
PMID:23274483
Abstract

Dorsal root ganglia (DRG) neurons spontaneously undergo robust neurite growth after axotomy. Long noncoding RNAs (lncRNAs) are an important class of pervasive genes involved in a variety of biological functions. However, the functions of lncRNAs in the regulation of responses of DRG neurons to injury stimuli remain untested. Here, lncRNA microarray analysis was performed to profile the lncRNAs in L4-L6 DRGs following rat sciatic nerve resection. The 105 lncRNAs were identified to be differentially expressed at 0, 1, 4, 7 d post injury. A coexpression network of 24 down-regulated lncRNAs and coding genes was constructed, and 115 targets of these 24 lncRNAs were found to be mainly involved in cell phenotype modulation, including glial cell migration, purinergic nucleotide receptor signaling pathway, vasodilation, regulation of multi-organism process, and neuropeptide signaling pathway, and also to be potentially associated with several key regeneration signaling pathways, including MAPK signaling pathway, and neuroactive ligand-receptor interaction. LncRNA BC089918 was selected from 24 down-regulated lncRNAs for validation by quantitative real-time polymerase chain reaction and in situ hybridization. And silencing of BC089918 with small interfering RNAs indicted that the lncRNA had a particular promoting effect on neurite outgrowth. Our data demonstrated a distinct involvement of lncRNAs in DRGs after nerve injury, thus contributing to illustration of molecular mechanisms responsible for nerve regeneration.

摘要

背根神经节 (DRG) 神经元在轴突切断后会自发地进行强烈的神经突生长。长链非编码 RNA (lncRNA) 是一类重要的普遍基因,参与多种生物学功能。然而,lncRNA 在调节 DRG 神经元对损伤刺激的反应中的作用尚未得到检验。在这里,进行了 lncRNA 微阵列分析,以描绘大鼠坐骨神经切除后 L4-L6 DRG 中的 lncRNA。在损伤后 0、1、4、7 天,鉴定出 105 个 lncRNA 表达差异。构建了一个下调的 24 个 lncRNA 和编码基因的共表达网络,发现这 24 个 lncRNA 的 115 个靶标主要参与细胞表型调节,包括神经胶质细胞迁移、嘌呤核苷酸受体信号通路、血管舒张、多器官过程的调节和神经肽信号通路,并且还可能与几个关键的再生信号通路有关,包括 MAPK 信号通路和神经活性配体-受体相互作用。从 24 个下调的 lncRNA 中选择 lncRNA BC089918 进行定量实时聚合酶链反应和原位杂交验证。用小干扰 RNA 沉默 BC089918 表明该 lncRNA 对神经突生长有特殊的促进作用。我们的数据表明 lncRNA 在神经损伤后的 DRG 中明显参与,从而有助于说明神经再生的分子机制。

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