Figure 4

Changes in miR-638 predicted target gene expression with mir-638 knockdown. (A) ECDF, (empirical cumulative distribution function) plot showing the t-statistics from empirical bayes-moderated t-tests for miR-638 predicted target genes (red) versus all genes (black). The predicted targets are shifted right from control in the inhibitor transfected samples, indicating the expected upregulation of target gene expression. Expression of the predicted targets are significantly different between controls and inhibitors by two-sided Kolmogorov-Smirnov tests (P-value = 2.576e-10). (B) Density plots of the t-statistics from correlations between miR-638 expression and gene expression in emphysematous lung tissue for: (1) all genes (black), (2) all miR-638 predicted targets (red), and (3) those miR-638 predicted targets over-expressed in fibroblasts with miR-638 knock-down (blue). The majority of miR-638 correlations are in the positive direction, consistent with the red line shifted right, while the targets over-expressed with miR-638 inhibition are mostly anti-correlated, consistent with the blue line shifted left. (C) A magnified view of the miR-638 row extracted from the expression matrix in Figure 4 shows the pathways positively and negatively correlated with miR-638 expression (red and blue, respectively). Pathways upregulated with miR-638 knock-down in fibroblasts are shown above this in blue. This illustrates that many of the pathways overlap, particularly in the sets of pathways associated with cell cycle progression, RNA transcription, and mitochondrial biogenesis (bar 1), and DNA repair (bar 2).