Methylation-Regulated Promoters (mrAPs) and Their Roles in Cell Signaling and Tumorigenesis

We defined 189 selective promoters that show a negative correlation between their activity and methylation status as methylation-regulated APs (mrAPs). The activity changes of mrAPs are significantly negatively correlated with their methylation levels (R = -0.76, p-value = 1.2e-13) (Figure 3-18 A). Functional enrichment analysis of genes with mrAPs revealed significant enrichment in cell signaling pathways such as MAPK cascade activation, vesicle-mediated transport regulation, Ras protein signal transduction, as well as tumor-related pathways including negative regulation of cell cycle, cell proliferation, and cell growth regulation (Figure 3-18 B). These findings suggest that these genes play important roles in multiple cell signaling pathways and may be closely associated with tumor initiation and progression.