Long non-coding RNA uc.217 regulates neurite outgrowth in dorsal root ganglion neurons following peripheral nerve injury
Long non-coding RNA uc.217 regulates neurite outgrowth in dorsal root ganglion neurons following peripheral nerve injury
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长非编码RNA uc.217调节周围神经损伤后背根神经节神经元的神经突生长
DOI：
10.1111/ejn.12966
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发表时间：
2015-07-01
影响因子：
3.4
通讯作者：
Yu, Bin
中科院分区：
文献类型：
--
作者：
Yao, Chun;Wang, Jing;Yu, Bin
坐骨神经损伤后，背根神经节（dorsal root ganglion， DRG）神经元的内在再生能力可被激活，周围神经再生是一个受多种分子反应和信号通路调控的复杂过程。长链非编码RNA （Long non-coding RNA, lncRNAs）是一种长度约为200个核苷酸的RNA转录物，不具有蛋白质编码潜能。它们在表观遗传、转录和转录后水平调节基因表达，因此参与许多生物过程和人类疾病。然而，lncrna在调节DRG神经元对坐骨神经损伤反应中的作用和机制尚未得到充分的研究。我们之前通过微阵列分析分析了大鼠坐骨神经横断后L4-6 DRGs中lncRNAs和mrna的表达谱，并构建了失调lncRNAs和编码基因的共表达网络。在这项研究中，这些失调的lncrna之一，如。217，详细研究其在再生DRG神经元生长中的表达变化和调控功能。实时荧光定量PCR和原位杂交证实了uc的表达。217在坐骨神经损伤后DRG神经元中表达下调。uc的沉默。小干扰RNA表达217可显著促进培养DRG神经元的神经突生长。此外，通过生物信息学分析和实验验证，确定了uc的几个潜在靶点。217个，参与调控DRG神经元的生长。总的来说，我们的研究结果表明，一种新的lncRNA，如。217，在周围神经再生中起重要的调节作用。
The intrinsic regeneration capacity of dorsal root ganglion (DRG) neurons can be activated after sciatic nerve injury, and peripheral nerve regeneration is a complex process regulated by multiple molecular responses and signaling pathways. Long non-coding RNAs (lncRNAs) are RNA transcripts >200 nucleotides in length without protein-coding potential. They regulate gene expression at epigenetic, transcriptional and post-transcriptional levels, and are thus involved in many biological processes and human diseases. However, the role and mechanisms of lncRNAs in regulating the responses of DRG neurons to sciatic nerve injury are not fully investigated. We have previously analysed the expression profiles of lncRNAs and mRNAs in L4-6 DRGs, following rat sciatic nerve transection, by microarray analysis, and constructed a coexpression network of dysregulated lncRNAs and coding genes. In this study, one of these dysregulated lncRNAs, uc.217, was chosen for detailed examination of its expression changes and regulative functions in regenerative DRG neuronal outgrowth. Quantitative real-time PCR and insitu hybridisation confirmed that the expression of uc.217 was down-regulated in DRG neurons after sciatic nerve injury. Silencing of uc.217 expression by small interfering RNA could significantly promote neurite outgrowth in cultured DRG neurons. Moreover, bioinformatic analysis and experimental validation were performed to identify several potential targets of uc.217, which were involved in the regulation of DRG neuron outgrowth. Collectively, our results suggested that a new lncRNA, uc.217, played an important regulative role in peripheral nerve regeneration.