Fig. 4

Significant dysregulation of canonical pathways observed through changes in expression of the mRNA targets of differentially expressed miRNAs. Experimentally verified and differentially expressed mRNA targets of differentially expressed miRNAs were analyzed using IPA to predict effects of miRNA-mRNA pairs on canonical pathways. A Heatmap displays canonical pathways that were predicted to be significantly dysregulated (B-H p-value < 0.01 across all doses) based upon differentially expressed mRNA targets. A positive z-score indicates predicted activation of the pathway based on gene expression and a negative z-score indicates predicted deactivation of the pathway based on gene expression. Pathways are hierarchically clustered by z-score. B Fold changes of inversely correlated miRNA-mRNA target pairs with involvement in the significantly dysregulated pathways. Three miRNAs had two mRNA targets each that were inversely correlated across all doses and significant in at least one condition