Fig. 1

Model and validation of miRNA-target coupling. a RNAs up and down regulate one another by titrating shared miRNA regulators. Up regulation of RNA B sequesters shared miRNAs, leading to weaker miRNA-mediated repression of RNA A transcripts and its consequent up regulation. b In order to validate predicted interaction networks on a large scale, we evaluated whether interactions are predictive of global mRNA expression changes following shRNA perturbations using LINCS. A selection of known cancer genes in breast cancer and c prostate adenocarcinomas were effectively repressed following silencing of their predicted ceRNA regulators in MCF7 and PC3, respectively. Red bars represent average fold changes of a target ceRNA relative to non-targeting controls (gray bars) following silencing of its predicted ceRNA regulators at select time points; see Figs. 2 and 3 for details. Data are represented as mean ± SEM