Figure 7.
PPARD upregulates EIF4G1 and CDK1 expression in IECs. A and B, EIF4G1 and CDK1 protein expression levels in IECs from PD (A) and ApcΔ580-PD (B) mice and their corresponding control littermates. C-E, EIF4G1 expression in human colorectal cancer invasive fronts. C, Representative EIF4G1 IHC staining images of human paired colorectal adenomas, CRC tumor centers, and CRC invasive fronts of 2 patients. D, Total combined CES of nucleus and cytoplasm IHC staining of EIF4G1 for the paired colorectal adenomas, CRC tumor centers, and CRC invasive fronts (n = 41 patients). E, Correlation analysis of PPARD and EIF4G1 IHC scores for invasive fronts from 41 patients. F, EIF4G1 mRNA expression level in human CRC organoid cells transfected with Ctrl-siRNA or PPARD siRNA for 48 hours. PPARD downregulation by siRNA decreased EIF4G1 mRNA expression in human CRC organoid cells. G, PPARD downregulation by siRNA decreased CDK1 mRNA expression in human CRC organoid cells as described in panel F. H, Effects of EIF4G1 inhibitor 4EGI-1 on PPARD promotion of CT26 mouse colon cancer cell invasion. CT26 cells stably transduced with a control (Ctrl) or mouse DDK-PPARD lentiviral particles were treated with 4EGI-1 (50μM) or vehicle solvent (DMSO) for 48 hours. Left: representative photomicrographs of invaded cells. Right: invaded cells in at least 4 random individual fields per insert membrane were counted. I, Effects of CDK1 inhibitor RO-3306 on PPARD promotion of colon cancer cell migration. CT26 mouse colon cancer cells stably transduced with control (Ctrl) or DDK-PPARD lentiviral particles were treated with RO3306 (8.0 μM) or vehicle solvent (DMSO) for 36 hours. Left: representative photomicrographs of migrated cells. Right: migrated cells in at least 4 random individual fields per insert membrane were counted. J, Conceptual scheme of pro-invasive pathways that are upregulated by PPARD to promote CRC progression and invasion. Data are shown as mean ± SEM. *P < 0.05, **P < 0.01, ***P < 0.001, and ****P < 0.001.