Identification of candidate genes and miRNAs associated with neuropathic pain induced by spared nerve injury
Identification of candidate genes and miRNAs associated with neuropathic pain induced by spared nerve injury
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DOI：
10.3892/ijmm.2019.4305
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发表时间：
2019-10-01
影响因子：
5.4
通讯作者：
Zhang, Chun-Guo
中科院分区：
文献类型：
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作者：
Li, He;Wan, Hong-Quan;Zhang, Chun-Guo
神经性疼痛 (NP) 是一种复杂的慢性疼痛，由影响体感神经系统的损伤或功能障碍引起。本研究旨在鉴定与 NP 相关的关键基因和 miRNA。微阵列数据（访问号 GSE91396）从基因表达综合库（GEO）下载。来自三个大脑区域的小鼠 RNA-seq 样本 [伏隔核 (NAc)；比较了幸存神经损伤（SNI）模型和假手术之间的内侧前额叶皮层（mPFC）和导水管周围灰质（PAG）]。数据标准化后，使用 limma 包筛选差异表达的 RNA，并使用注释、可视化和集成发现数据库进行功能富集分析。使用Cytoscape软件构建了microRNA（miRNA/miR）-mRNA调控网络和miRNA-靶基因-通路调控网络。与假手术组相比，SNI 模型中总共鉴定出 2,776 个差异表达 RNA（219 个 miRNA 和 2,557 个 mRNA）。通过对三个大脑区域的 2,325 个常见差异表达 RNA 进行加权基因共表达网络分析 (WGCNA)，总共发现两个重要模块（红色和绿松石模块）与 NP 相关。 miRNA-mRNA 调控网络中的差异表达基因 (DEG) 在 21 个基因本体术语和 5 个通路中显着富集。根据miRNA靶基因通路调控网络，总共发现4个重要的DEG（CXCR2、IL12B、TNFSF8和GRK1）和5个miRNA（miR-208a-5p、miR-7688-3p、miR-344f-3p、miR-135b-3p和miR-135a-2-3p）与NP相关。四个重要的 DEG（CXCR2、IL12B、TNFSF8 和 GRK1）和 5 个 miRNA（miR-208a-5p、miR-7688-3p、miR-344f-3p、miR-135b-3p 和 miR-135a-2-3p）在 SNI 中差异表达，表明它们在 NP 发病机制中可能发挥作用。
Neuropathic pain (NP) is a complex, chronic pain condition caused by injury or dysfunction affecting the somatosensory nervous system. This study aimed to identify crucial genes and miRNAs involved in NP. Microarray data (access number GSE91396) were downloaded from the Gene Expression Omnibus (GEO). Murine RNA-seq samples from three brain regions [nucleus accumbens, (NAc); medial prefrontal cortex, (mPFC) and periaqueductal gray, (PAG)] were compared between the spared nerve injury (SNI) model and a sham surgery. After data normalization, differentially expressed RNAs were screened using the limma package and functional enrichment analysis was performed with Database for Annotation, Visualization and Integrated Discovery. The microRNA (miRNA/miR)-mRNA regulatory network and miRNA-target gene-pathway regulatory network were constructed using Cytoscape software. A total of 2,776 differentially expressed RNAs (219 miRNAs and 2,557 mRNAs) were identified in the SNI model compared with the sham surgery group. A total of two important modules (red and turquoise module) were found to be related to NP using weighed gene co-expression network analysis (WGCNA) for the 2,325 common differentially expressed RNAs in three brain regions. The differentially expressed genes (DEGs) in the miRNA-mRNA regulatory network were significantly enriched in 21 Gene Ontology terms and five pathways. A total of four important DEGs (CXCR2, IL12B, TNFSF8 and GRK1) and five miRNAs (miR-208a-5p, miR-7688-3p, miR-344f-3p, miR-135b-3p and miR-135a-2-3p) were revealed according to the miRNA-target gene-pathway regulatory network to be related to NP. Four important DEGs (CXCR2, IL12B, TNFSF8 and GRK1) and five miRNAs (miR-208a-5p, miR-7688-3p, miR-344f-3p, miR-135b-3p and miR-135a-2-3p) were differentially expressed in SNI, indicating their plausible roles in NP pathogenesis.