Identification of the Spinal Expression Profile of Non-coding RNAs Involved in Neuropathic Pain Following Spared Nerve Injury by Sequence Analysis.
Identification of the Spinal Expression Profile of Non-coding RNAs Involved in Neuropathic Pain Following Spared Nerve Injury by Sequence Analysis.
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DOI：
10.3389/fnmol.2017.00091
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发表时间：
2017
影响因子：
4.8
通讯作者：
Fan Y
中科院分区：
文献类型：
--
作者：
Zhou J;Xiong Q;Chen H;Yang C;Fan Y
神经病理性疼痛（NP）是由神经系统损伤引起的异常疼痛，其与感觉通路中的基因表达变化有关。然而，分子机制尚未完全理解。非编码核糖核酸（ncRNA）是不翻译成蛋白质的RNA分子。NcRNA参与许多细胞过程，并且体内库的突变或不平衡可导致多种疾病。虽然ncRNA最近已被证明在NP发病机制中发挥作用，但ncRNA在NP中的具体作用在很大程度上仍然未知。在这项研究中，进行测序分析，以调查在脊髓中的ncRNA的表达模式后，备用神经损伤诱导的NP。在保留神经损伤（SNI）手术后14天，总共有134种长非编码RNA（lncRNA）、12种microRNA（miRNAs）、188种环状RNA（circRNA）和1066种mRNA被显著调节。接下来，进行定量实时聚合酶链反应（PCR）以验证所选lncRNA、miRNA、circRNA和mRNA的表达。利用生物信息学工具和数据库来探索潜在的ncRNA功能和关系。结果表明，核糖体、PI 3 K-Akt信号通路、粘着斑、ECM-受体相互作用、阿米巴病和蛋白质消化吸收是SNI发病机制中最重要的通路。此外，还构建了NP的lncRNA-miRNA-mRNA和circRNA-miRNA-mRNA网络。这是第一个研究，以全面确定调节ncRNA的脊髓，并证明参与不同的ncRNA表达模式的脊髓NP的发病机制，通过序列分析。这些信息将使进一步研究NP的发病机制，并促进开发新的NP治疗靶向ncRNA。
Neuropathic pain (NP) is caused by damage to the nervous system, resulting in aberrant pain, which is associated with gene expression changes in the sensory pathway. However, the molecular mechanisms are not fully understood. A non-coding Ribose Nucleic Acid (ncRNA) is an RNA molecule that is not translated into a protein. NcRNAs are involved in many cellular processes, and mutations or imbalances of the repertoire within the body can cause a variety of diseases. Although ncRNAs have recently been shown to play a role in NP pathogenesis, the specific effects of ncRNAs in NP remain largely unknown. In this study, sequencing analysis was performed to investigated the expression patterns of ncRNAs in the spinal cord following spared nerve injury-induced NP. A total of 134 long non-coding RNAs (lncRNAs), 12 microRNAs (miRNAs), 188 circular RNAs (circRNAs) and 1066 mRNAs were significantly regulated at 14 days after spared nerve injury (SNI) surgery. Next, quantitative real-time polymerase chain reaction (PCR) was performed to validate the expression of selected lncRNAs, miRNAs, circRNAs, and mRNAs. Bioinformatics tools and databases were employed to explore the potential ncRNA functions and relationships. Our data showed that the most significantly involved pathways in SNI pathogenesis were ribosome, PI3K-Akt signaling pathway, focal adhesion, ECM-receptor interaction, amoebiasis and protein digestion and absorption. In addition, the lncRNA-miRNA-mRNA and circRNA-miRNA-mRNA network of NP was constructed. This is the first study to comprehensively identify regulated ncRNAs of the spinal cord and to demonstrate the involvement of different ncRNA expression patterns in the spinal cord of NP pathogenesis by sequence analysis. This information will enable further research on the pathogenesis of NP and facilitate the development of novel NP therapeutics targeting ncRNAs.