Integrated Analysis of miRNA and mRNA Expression Profiles Reveals the Molecular Mechanism of Posttraumatic Stress Disorder and Therapeutic Drugs

Purpose: Post-traumatic stress disorder (PTSD) is a result of trauma exposure and is related to psychological suffering as a long-lasting health issue. Further analysis of the networks and genes involved in PTSD are critical to the molecular mechanisms of PTSD. Methods: In this study, we aimed to identify key genes and molecular interaction networks involved in the pathogenesis of PTSD by integrating mRNA and miRNA data. Results: By integrating three high-throughput datasets, 5606 differentially expressed genes (DEGs) were detected, including five differentially expressed miRNAs (DEmiRNAs) and 5525 differentially expressed mRNAs (DEmRNAs). Nineteen upregulated and 46 downregulated DEmRNAs were identified in both GSE64813 and GSE89866 datasets, while five upregulated DEmiRNAs were found in the GSE87768 dataset. Functional annotations of these DEmRNAs indicated that they were mainly enriched in blood coagulation, cell adhesion, platelet activation, and extracellular matrix (ECM)-receptor interaction. Integrated protein-protein and miRNA-protein interaction networks among the DEGs were established with the help of 65 nodes and 121 interactions. Finally, 286 small molecules were obtained based on the Drug-Gene Interaction database (DGIdb). Three genes, prostaglandin-endoperoxide synthase 1 (PTGS1), beta-tubulin gene (TUBB1), and cyclin-dependent kinase inhibitor lA (CDKN1A), were the most promising targets for PTSD therapy. Additionally, the present study also provided a higher performance diagnostic model for PTSD based on 17 DEmRNAs, which was validated in two independent datasets, GSE109409 and GSE63878. Conclusion: Our data provides a new molecular aspect that ECM-receptor interaction and the platelet activation process could be the potential molecular mechanism of PTSD, and the genes involved in this process may be promising therapeutic targets. A higher-performance diagnostic model for PTSD has also been identified.