Figure 3

EMT-specific miRNA-target relationships directly and indirectly regulated by SOX2 in 2102Ep and NTera-2 cells. (A) This Venn diagram displays the exclusive and mutual expression of all ≥2-fold up or downregulated genes in 2102Ep and NTera-2 cells after SOX2 knock-down. Excluded from the mutual group were the four oppositely deregulated genes. As shown, despite a large overlap between the two cell lines, significantly more genes were deregulated in 2102Ep cells than NTera-2 cells. (B) This chart displays the expression levels of all 26 EMT genes differentially expressed in 2102Ep and NTera-2 cells combined. Those denoted in red are targets of the 11 miRNAs in Table 2 as predicted by our analysis. Several of these were previously validated. Together with SOX2 these miRNAs and targets form a complex network of EMT regulation (C). The EMT network compiled from predicted miRNA and gene interaction data from this study and previously established interactions. The thick arrows represent previously validated functional relationships, which include those predicted by this study, while the thin arrows are novel relationships predicted by this study alone. Red arrows represent transcriptional control by SOX2. Stripes without arrowheads or bars represent the previously validated transcriptional activation by SOX2 of genes that could be transcriptionally inhibited by SOX2 in our study. SOX2 binding sites were also found in the promoter regions of HAS2 and ZEB2 as per the ChIP data from Lister et al. and Boyer et al.[11, 12].