miRNA targetome associated with early relapse in high grade serous ovarian cancer

Background: High-grade serous ovarian cancer (HGSOC) is the most lethal subtype of ovarian cancer due to the high rate of early relapse and resistance to chemotherapy. MicroRNAs (miRNAs) control the post-transcriptional expression of a substantial number of coding genes related to ovarian cancer. Therefore, a great interest in the discovery of miRNA-based therapeutics drives many researchers in the field. To identify relevant targets for miRNA-based therapeutics, in this study we analyzed the miRNA targetome associated with early relapse in HGSOC. Methods: : Four Gene Expression Omnibus (GEO) datasets were analyzed by GEO2R to find differentially expressed miRNAs (DEMs) in early relapse patients. The miRDB tool was used to predict the gene targets of the DEMs. Functional annotation and cluster analysis was performed on Database for Visualization and Integrated Discovery and Metascape to identify biological processes enriched in the miRNA targetome. To verify the prognostic role of the key miRNA targets, Kaplan-Meier survival analysis was conducted in a validation dataset curated from The Cancer Genome Atlas and GEO datasets on KM-Plotter. A protein-protein interaction network of the prognostic miRNA targets was constructed on STRING. Network analysis was performed on Cytoscape to find the genes with the highest degree and centrality. The interactors and pathways associated with the key miRNA-target genes were searched on inBio Discover. Results: : We identified a wide miRNA targetome with fifteen common miRNA targets associated with early relapse in HGSOC. These miRNA targets were enriched in biological processes associated with “transcription from RNA polymerase II promoter”. Further analysis on the validation set verified the prognostic role of thirteen of these targets in HGSOC. The network analysis revealed CWC27, DCUN1D1 , MEF2C , and SPOPL as the central miRNA targets associated with early relapse. The primary interactor hubs of these four genes were involved in processes that regulate the synthesis or cleavage of other gene products, further expanding the scope of impact of the miRNA targetome. Conclusions: : We believe that the four miRNA targets we identified in this study may be potential targets of miRNA-based therapeutics to prevent early relapse in HGSOC.