Identifying the Biomarkers of Spinal Cord Injury and the effects of Neurotrophin-3 Based on MicroRNA and mRNA Signature

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Abstract Background To gain a better understanding of the molecular mechanisms of spinal cord injury and the effects of Neurotrophin-3, differentially expressed microRNAs (DEmiRNAs) and genes (DEGs) were analyzed. Methods The miRNA transcription profile of GSE82195 and the mRNA transcription profile of GSE82196 were downloaded from the Gene Expression Omnibus (GEO). Then, DERs were identified using limma. The noise-robust soft clustering of the intersection DERs was performed using Mfuzz package. Additionally, the integrated miRNAs–targets regulatory network was constructed using Cytoscape. Finally, the Comparative Toxicogenomics Database 2019 update was used to search the central nervous system injury related pathway. Results A total of 444 DERs including 382 DEGs and 62 DEmiRNAs were screened between group injury and group none whlie 576 DERs including 523 DEGs and 55 DEmiRNAs were screened between group NT-3 and group injury. Moreover, 80 intersections DERs were identified. DREs in cluster 1 were firstly significantly down-regulated in group injury and subsequently were significantly up-regulated in group NT-3. DERs in cluster 2 were firstly up-regulated in group injury and subsequently down-regulated in group NT-3. OPRL1 and GHSR were enriched in the KEGG pathway of Neuroactive ligand-receptor interaction. OPRL1 was involved in the chemical homeostasis and ion homeostasis while GHSR was related to the regulation of fatty acid metabolic process and regulation of cellular ketone metabolic process. Conclusion rno-miR-3072 and rno-miR-667-5p and OPRL1 and GHSR might participate in the pathogenesis of neurological injury and the neurotrophin-3 treatment.

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