Genome expression profiling predicts the molecular mechanism of peripheral myelination.

Abstract

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.