Dissecting the shared molecular mechanisms underlying polycystic ovary syndrome and schizophrenia etiology: A translational integrative approach

Abstract

Recent evidence suggests that individuals with polycystic ovary syndrome (PCOS) have an increased risk of developing mental health disorders and comorbidities linked to nervous system dysfunction. Interestingly, patients with schizophrenia (SCZ) often exhibit PCOS symptoms, indicating a possible connection between the two conditions. However, the underlying molecular links between these diseases remain poorly understood. We employed a comprehensive in-silico approach, utilizing publicly available datasets to investigate shared biomarkers candidates and key regulators involved in the development of PCOS and SCZ. We retrieved the datasets from the NCBI GEO database and differentially expressed genes (DEGs) were identified for each dataset. Common DEGs (cDEGs) were determined, and transcription factors (TFs) and miRNA targeting cDEGs were examined using the mirDIP portal and TRRUST database, respectively. We also assessed the TF-miRNA interactions by TransmiR database and constructed a regulatory network including TFs-microRNAs-cDEGs. Our analysis identified a total of 15 cDEGs that are regulated by 15 TFs and 8 mRNAs. Among our findings, we prioritized RELA as a potential TF regulator for both diseases, demonstrating synergistic interaction with four cDEGs (EGR1, CXCL8, IL1RN, IL1B) and seven microRNAs (hsa-miR-580, hsa-miR-5695, hsa-miR-936, hsa-miR-3675, hsa-miR-634, hsa-miR-603, hsa-miR-222) that target these genes. Our data highlights potential common biomarkers for PCOS and SCZ, presenting a novel regulatory network that elucidates the molecular mechanisms underlying both conditions. This emphasizes the importance of further research to explore new translational approaches, which may ultimately lead to improved diagnostic and therapeutic strategies for affected individuals.