Overall, genes with which DM sites were associated include (but are not limited to) those having functions in chromatin compaction (NAT15; HDAC4; UHRF1); DNA damage/repair or chromosomal segregation (SOD3; UHRF1; NAT15); muscle contraction (NR4A3; HDAC4; FEZ1; PRKG1; KCNH7); axonal bundling/outgrowth (FEZ1); cell signaling in muscle (NR4A3; PRKG1); neuronal excitability/synaptic transmission (BDNF; BZRAP1; EPHA5
; KCNH7); muscle maturation (HDAC4); response to oxidative stress (SOD3); and inflammatory processes (AXL; SH2B2).
A TaqMan [R] probe/primer set was designed for real-time reverse transcription-PCR (RT-PCR) for the detection and quantification of gene expression of all currently known human members of the Eph receptor and ephrin family except for EphA5 and EphA10.
All currently known human Eph receptors and ephrins were investigated except EphA5 (assay design failed repeatedly) and EphA10 (sequence only recently reported) (20).
Expression in glioblastomas has been reported only for EphA5 (34).
Based on GO_BP and KEGG pathway enrichment analysis (Table 2), we found genes related to MAPK signaling pathway, insulin signaling pathway, axon guidance, focal adhesion, and energy pathways dysregulated in blood and brain, such as AKT1, TGFBR1, IGF1R, EPHA5, VCAM1, and L1CAM.
Term Count P value Genes MAPK signaling pathway 13 0.0062 RPS6KA5, AKT1, MAP4K4, MAP3K5, PLA2G4A, DUSP2, FGF9, TGFBR1, MAP2K4, MKNK2, PPP3R1, FGF12, DUSP6 Endocytosis 10 0.010 IGF1R, ADRB3, FLT1, TGFBR1, PSD3, VPS4B, DNAJC6, PSD2, ARAP2, LDLRAP1 Axon guidance 7 0.042 EPHA5, SEMA6A, PLXNA1, PPP3R1, SEMA4C, L1CAM, SRGAP1 Insulin signaling 6 0.0076 AKT1, L1CAM, IGF1R, IRS2, pathway SOCS7, RHOQ Focal adhesion 4 0.021 VCAM1, L1CAM, ITGA4, CERCAM Table 2: Small molecules which might reverse the dysregulation of AD in EC and HIP regions.