Identification of potential miRNA-mRNA regulatory network contributing to pathogenesis of polycystic ovarian syndrome

BackgroundPolycystic ovarian syndrome (PCOS), a gynae-endocrine disorder, has a relatively high risk of differential expression of miRNA (DE-miRNA) in the disease progression.AimsTo identify the DE-miRNA in the progression of PCOS in the ovarian cumulus cells.MethodsThe microarray dataset GSE72274 was analysed for PCOS-associated DE-miRNAs. miRNet identifies the target genes. Protein-protein interaction (PPI) network was constructed and hub genes were analysed by topology and module analysis. Transcription factors (TFs) and protein kinases (PKs) regulating the hub genes were identified using X2K tool. Biological functions were analysed using DAVID software. Finally, the DGIdb drug-gene interaction tool identifies the candidate medications.ResultsA total of 1577 DE-miRNAs linked to PCOS were identified, with 13 meeting the specified criteria. Subsequently, its 2053 target genes were retrieved through miRNet. Topology and module analysis identified the hub genes VEGFA, SOX2, KRAS, AKT1, and SMAD4 that are implicated in ovarian regulation. Notably, the study highlighted the significant role of the wnt signalling pathway, which is involved in ovarian function, specifically in follicle development, corpus luteum formation, and steroid production. Additionally, six TFs and PKs were identified as important regulators of these hub genes, and the potential medication interactions identified 11 medicines for VEGFA, KRAS, AKT1, and SMAD4 genes, while no suitable drug for SOX2 was identified.ConclusionIdentified, hub genes are known to associate with the regulation of ovarian function such as oocyte development, and steroid synthesis via the wnt signalling pathway.