Network-based integration of multi-omics data identifies the determinants of miR-491-5p effects

The identification of miRNAs’ targets and associated regulatory networks might allow the definition of new strategies using drugs whose association might mimic a given miRNA’s effects. Based on this assumption our group devised a multi-omics approach in an attempt to precisely characterize miRNAs’ effects. We combined the analysis of miR-491-5p direct targets, and effects at the transcriptomic and proteomic levels. We thus constructed an interaction network which enlightened highly connected nodes, being either direct or indirect targets of miR-491-5p effects: the already known EGFR and BCL2L1, but also EP300, CTNNB1 and several small-GTPases. By using different combinations of specific inhibitors of these nodes, we could greatly enhance their respective cytotoxicity and mimic miR-491-5p-induced phenotype. Our methodology thus constitutes an interesting strategy to comprehensively study the effects of a given miRNA. Also, we identified targets for which pharmacological inhibitors are already available for a clinical use, or in clinical trial phases. This study might thus enable innovative therapeutic options for ovarian cancer, which remains the first cause of death from gynecological malignancies in developed countries.