Genome-wide CRISPR-Cas9 screening identifies that hypoxia-inducible factor-1a-induced CBX8 transcription promotes pancreatic cancer progression via IRS1/AKT axis

Figure 5 CBX8 promotes pancreatic cancer cell proliferation by targeting IRS1/PI3K pathway. A: Differently expressed genes (DEGs) after CBX8 knockdown; B: KEGG pathway analysis of DEGs; C: Heatmap indicating the top 30 DEGs; D: Chromatin immunoprecipitation (ChIP)-Seq summary plot of CBX8-binding intensities across CBX8 peaks in BXPC-3 cells; E: Multiple tracks in the IGV diagram exhibited the co-occupancy of CBX8 and H3K27ac in the IRS1 enhancer region; F: Expression level of IRS1 mRNA was evaluated and normalized to the control group; G: Expression level of IRS1 mRNA was evaluated and normalized to untransduced controls; H: Expression of CBX8 and IRS1 exhibited a positive correlation in PC tissues; I: Luciferase reporter assay was performed to confirm the binding of CBX8 to the promoter region of IRS1 in 293T cells; J: ChIP-qPCR analysis was used to determine the binding affinity of CBX8 to IRS1 promoter regions; K: Expression of PTEN and PI3Kγ and the phosphorylation levels of IRS1, AKT, and mTOR in PC cells were assessed by Western blot. ^aP < 0.05, ^bP < 0.01.