Correlation analysis for selected miRNA/mRNA pairs and RNA-interaction modules. A) miRNA/mRNA correlation distributions obtained by selecting only those miRNAs that are responsible for the light vertical stripes in Figure 2A. B) miRNA/mRNA correlation distributions obtained by merging pairs-selection criteria applied in Figure 1C and Figure 3A. In details, among all possible miRNA/mRNA pairs, we selected only those involving mRNAs and miRNAs as follows: i. mRNAs characterized by a high correlation with at least one lncRNA in the normal tissues; ii. miRNAs responsible for the light vertical stripes in Figure 2A. Distributions are plotted as a function of different correlation thresholds, as indicated in the inset, for normal (left) and cancer dataset (right). The two peaks clearly visible in panel B (left) identify two ways of mRNA/miRNA interaction: one leading to a negative Pearson correlation between them; one leading to a positive Pearson correlation between them. Correspondingly, we defined two sponge modules: C) the pure sponge module, where the mRNA/miRNA correlation is negative; D) the mixed TF-sponge module, where the mRNA/miRNA correlation is positive and could be due to the presence of a repressor TF. In both cases, the lncRNA and the mRNA compete for miRNA binding (panels C and D, center). In the panels C and D (right), the valve symbols provide a schematic representation of the regulatory circuit: C) the mRNA (blue circle) concentration is due to the presence of the miRNA (valve) that is in turn regulated by the lncRNA (red circle); D) the mRNA (blue circle) concentration is due to the presence of a repressor TF regulated by the miRNA that is in turn regulated by the lncRNA.