Construction of miRNA-mRNA Regulatory Network Based on Differentially Expressed Genes in Traumatic Brain Injury Rats with Antidepressant Treatment

Background: Traumatic brain injury (TBI) is a complex pathology caused by external forces that leads to brain dysfunction, mental disorders, and other complications. Currently, there are no specific drugs for treating TBI-induced mental disorders, and conventional antidepressants fail to significantly improve patient outcomes. MicroRNAs (miRNAs) play crucial roles in brain dysfunction, but their contribution to TBI-related mental disorders remains unclear. Methods: We obtained microarray datasets from the Gene Expression Omnibus (GEO) database. The regulatory relationships between miRNAs and mRNAs were retrieved from the RAID v2.0 ncRNAs database. Differentially expressed genes (DEGs) and miRNAs (DE-mis) were identified using the R package 'limma'. Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to determine the functional roles of DEGs in TBI. Finally, a miRNA-mRNA interaction network was constructed using Cytoscape, and core regulatory pairs were identified through topological analysis. Results: We identified 1,019 DEGs from GSE115614 and 130 DE-mis from GSE129373. GO annotation and KEGG pathway enrichment analyses revealed that DEGs were significantly enriched in ribosomal synthesis, synaptic development, protein binding, and multiple signaling pathways including salivary secretion and thyroid hormone signaling. We constructed a regulatory network comprising 16 miRNAs and 175 mRNAs. Further topological analysis identified six key regulatory pairs that potentially play critical roles in the pathophysiology of TBI-associated mental disorders. Conclusions: This study established a comprehensive miRNA-mRNA regulatory network associated with mental disorders in TBI rats and identified six key regulatory pairs that could serve as potential therapeutic targets. Future in vivo and in vitro studies are warranted to validate these findings and explore their therapeutic implications.