Department of Radiology, Jinhua People's Hospital, Jinhua, Zhejiang 321000, P.R. China.
Int J Mol Med. 2018 Mar;41(3):1500-1508. doi: 10.3892/ijmm.2017.3348. Epub 2017 Dec 22.
The present study aimed to explore the molecular mechanism of myelination in the peripheral nervous system (PNS) based on genome expression profiles. Microarray data (GSE60345) was acquired from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were integrated and subsequently subjected to pathway and term enrichment analysis. A protein‑protein interaction network was constructed and the top 200 DEGs according to their degree value were further subjected to pathway enrichment analysis. A microRNA (miR)‑target gene regulatory network was constructed to explore the role of miRs associated with PNS myelination. A total of 783 upregulated genes and 307 downregulated genes were identified. The upregulated DEGs were significantly enriched in the biological function of complement and coagulation cascades, cytokine‑cytokine receptor interactions and cell adhesion molecules. Pathways significantly enriched by the downregulated DEGs included the cell cycle, oocyte meiosis and the p53 signaling pathway. In addition, the upregulated DEGs among the top 200 DEGs were significantly enriched in natural killer (NK) cell mediated cytotoxicity and the B cell receptor (BCR) signaling pathway, in which Fc γ receptor (FCGR), ras‑related C3 botulinum toxin substrate 2 (RAC2) and 1‑phosphatidylinositol‑4,5‑bisphosphate phosphodiesterase γ‑2 (PLCG2) were involved. miR‑339‑5p, miR‑10a‑5p and miR‑10b‑5p were identified as having a high degree value and may regulate the target genes TOX high mobility group box family member 4 (Tox4), DNA repair protein XRCC2 (Xrcc2) and C5a anaphylatoxin chemotactic receptor C5a2 (C5ar2). NK cell mediated cytotoxicity and the BCR pathway may be involved in peripheral myelination by targeting FCGR, RAC2 and PLCG2. The downregulation of oocyte meiosis, the cell cycle and the cellular tumor antigen p53 signaling pathway suggests decreasing schwann cell proliferation following the initiation of myelination. miR‑339‑5p, miR‑10a‑5p and miR‑10b‑5p may play important roles in PNS myelination by regulating Tox4, Xrcc2 and C5ar2.
本研究旨在基于基因组表达谱探索周围神经系统(PNS)髓鞘形成的分子机制。从基因表达综合数据库中获取微阵列数据(GSE60345)。整合差异表达基因(DEGs),并进行通路和术语富集分析。构建蛋白质-蛋白质相互作用网络,并根据度值进一步对前 200 个 DEGs 进行通路富集分析。构建 microRNA(miR)-靶基因调控网络,探讨与 PNS 髓鞘形成相关的 miRs 的作用。共鉴定出 783 个上调基因和 307 个下调基因。上调的 DEGs 显著富集于补体和凝血级联、细胞因子-细胞因子受体相互作用和细胞黏附分子的生物学功能中。下调的 DEGs 显著富集的通路包括细胞周期、卵母细胞减数分裂和 p53 信号通路。此外,前 200 个上调的 DEGs 显著富集于自然杀伤(NK)细胞介导的细胞毒性和 B 细胞受体(BCR)信号通路,其中 Fcγ受体(FCGR)、ras 相关 C3 肉毒毒素底物 2(RAC2)和 1-磷酸肌醇-4,5-二磷酸磷酸二酯酶γ-2(PLCG2)参与其中。miR-339-5p、miR-10a-5p 和 miR-10b-5p 被鉴定为具有高程度值,可能调节靶基因 TOX 高迁移率族框家族成员 4(Tox4)、DNA 修复蛋白 XRCC2(Xrcc2)和 C5a 过敏毒素趋化因子受体 C5a2(C5ar2)。NK 细胞介导的细胞毒性和 BCR 通路可能通过靶向 FCGR、RAC2 和 PLCG2 参与周围髓鞘形成。卵母细胞减数分裂、细胞周期和细胞肿瘤抗原 p53 信号通路的下调表明,髓鞘形成启动后 Schwann 细胞增殖减少。miR-339-5p、miR-10a-5p 和 miR-10b-5p 通过调节 Tox4、Xrcc2 和 C5ar2 可能在 PNS 髓鞘形成中发挥重要作用。