Investigate synergistic and competitive regulation between miRNAs by using a multivariate information measurement

Multiple microRNAs can bind to the 3' untranslated region (3'UTR) of the same mRNA transcript. Depending on the spatial arrangement of their binding sites, endogenous microRNAs may cooperate to enhance repression or compete for overlapping sites. Although synergistic and competitive miRNA regulation has been proposed, it remains incompletely characterized. Here, we introduce a computational framework based on the partial information decomposition (PID) measurement to quantify implicit interaction effects between microRNA pairs. By integrating sequence-based targeting features with expression data, our approach infers putative synergistic or competitive relationships between microRNAs. We applied the method to TargetScan predictions and The Cancer Genome Atlas (TCGA) datasets. We found that miRNA pairs with neighboring binding sites are more likely to exhibit synergistic behavior, whereas pairs with overlapping binding sites more frequently show competitive behavior, particularly when the miRNAs display high functional similarity and the corresponding miRNA-mRNA-miRNA triplet yields a positive or negative synergy-redundancy score. Taken together, these results provide a systematic strategy to map cooperative and competitive miRNA interactions and contribute to a deeper understanding of the miRNA-mRNA regulatory landscape.