Altered long noncoding RNA expressions in dorsal root ganglion after rat sciatic nerve injury
Altered long noncoding RNA expressions in dorsal root ganglion after rat sciatic nerve injury
复制标题
大鼠坐骨神经损伤后背根神经节长非编码RNA表达的改变
DOI：
10.1016/j.neulet.2012.12.014
复制
发表时间：
2013-02-08
影响因子：
2.5
通讯作者：
Gu, Xiaosong
中科院分区：
文献类型：
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作者：
Yu, Bin;Zhou, Songlin;Gu, Xiaosong
背根神经节(DRG)神经元在轴突切断后自发生长旺盛。长非编码RNA(Long Non Coding RNAs，LncRNAs)是一类重要的普遍存在的基因，参与多种生物学功能。然而，LncRNAs在调节DRG神经元对损伤刺激的反应中的作用仍未得到验证。在这里，我们用LncRNA芯片分析了大鼠坐骨神经切除后L4-L6背根节中的LncRNAs。在伤后0、1、4、7d分别鉴定出差异表达的105个lncRNAs。构建了一个由24个下调的lncRNAs和编码基因组成的共表达网络，其中115个靶基因主要参与细胞表型调节，包括胶质细胞迁移、嘌呤能核苷酸受体信号通路、血管扩张、多生物过程调节和神经肽信号通路，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个表达下调的LncRNA中筛选出BC089918，通过实时定量聚合酶链式反应和原位杂交进行验证。用小干扰RNA沉默BC089918细胞表明，lncRNA对轴突生长有特殊的促进作用。我们的数据表明，在神经损伤后，LncRNAs明显参与了DRG，从而有助于阐明神经再生的分子机制。(C)2012爱思唯尔爱尔兰有限公司。保留所有权利。
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. (C) 2012 Elsevier Ireland Ltd. All rights reserved.