Network Analysis of miRNA and mRNA Changes in the Prelimbic Cortex of Rats With Chronic Neuropathic Pain: Pointing to Inflammation
Network Analysis of miRNA and mRNA Changes in the Prelimbic Cortex of Rats With Chronic Neuropathic Pain: Pointing to Inflammation
复制标题
慢性神经病理性疼痛大鼠前缘皮层 miRNA 和 mRNA 变化的网络分析：指向炎症
DOI：
10.3389/fgene.2020.00612
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发表时间：
2020-06-23
影响因子：
3.7
通讯作者：
Wu, Shengxi
中科院分区：
文献类型：
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作者：
Cai, Guohong;Zhu, Yuanyuan;Wu, Shengxi
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 NP 大鼠前边缘皮质 (PL) 中的关键 mRNA 和 microRNA (miRNA)。本研究应用了 mRNA 和 miRNA 微阵列。通过独创性途径分析（IPA）构建了 miRNA-mRNA 调控网络。与对照组相比，幸免神经损伤（SNI）组共鉴定出 35 个差异表达（DE）RNA（24 个 miRNA 和 10 个 mRNA）。 DE miRNA-mRNA网络显示IL-6和肿瘤坏死因子(TNF)是核心成分。 Mir-30c-5p 和 mir-16-5p 是网络中连接最紧密的 miRNA。有趣的是，四种表达量显着增加的 mRNA（Rnase 4、Egr2、Rexo4 和 Klf2）在小胶质细胞中大量表达，这一点通过实时定量聚合酶链反应（qPCR）得到验证。此外，M1 极化巨噬细胞中 Rnase4 和 Egr2 的表达减少，而 M2 极化巨噬细胞中 Rnase4 和 Egr2 的表达增加。总之，我们在 SNI 大鼠的 PL 中筛选了数十种 DE mRNA 和 miRNA。 DE mRNA 和 miRNA 网络的核心指向与炎症相关的分子。四种 mRNA（Rnase4、Egr2、Rexo4 和 Klf2）可能是 M2 极化的潜在标记。
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 mRNAs and microRNAs (miRNAs) in the prelimbic cortex (PL) of NP rats. mRNA and miRNA microarrays were applied in the present study. The miRNA-mRNA regulatory network was constructed by using ingenuity pathway analysis (IPA). A total of 35 differentially expressed (DE) RNAs (24 miRNAs and 10 mRNAs) were identified in the spared nerve injury (SNI) group compared with the control group. The DE miRNA-mRNA network showed that IL-6 and tumor necrosis factor (TNF) were core components. Mir-30c-5p and mir-16-5p were the most connected miRNAs in the network. Interestingly, four mRNAs (Rnase 4, Egr2, Rexo4, and Klf2) with significantly increased expression were abundantly expressed in microglia, which was verified by the real-time quantitative polymerase chain reaction (qPCR). Furthermore, the expression of Rnase4 and Egr2 decreased in M1-polarized macrophages and increased in M2-polarized macrophages. In conclusion, we screened dozens of DE mRNAs and miRNAs in the PL of SNI rats. The core of the DE mRNA and miRNA network pointed to molecules associated with inflammation. Four mRNAs (Rnase4, Egr2, Rexo4, and Klf2) might be the potential markers of M2 polarization.