TGR-1202 and carfilzomib inhibits c-Myc–dependent gene transcription. (A) GSEA of c-Myc target genes in LY10 cells treated by the TC combination. The x-axis represents the listed genes ranked from most upregulated to most downregulated. The y-axis indicates RESs. All the 4 gene sets reached their peak RES score at the end of ranked gene list, indicating that the drug combination of TG and Cfz exhibits a negative effect on the transcription of c-Myc targets. (B) LY10 and LY7 cells were treated as indicated for 24 hours then processed for western blot against 2 known targets of c-Myc, namely eIF4B and E2F1. (C) The χ2 test was performed to compare Myc and E2F1 gene sets enriched and not enriched for transcriptional downregulation in cells treated by the TC and IB drug combinations. GS29, Schlosser_Myc_Targets; GS32, Kim_Myc_Targets; GS52, Schuhmacher_Myc_Targets; GS70, Dang_Regulated_By_Myc.
