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. 2023 Dec 15;133(24):e168670. doi: 10.1172/JCI168670

Figure 6. Activation of ADORA2A signaling confers an NE-lineage biased transcription profile to PCa cells.

Figure 6

(A) The cut & tag data show a repressed H3K27ac level in LNCaP/AR-ADORA2A cells upon the stimulation of CGS (n = 2 independent experiments). (B and C) Cut & tag results indicate that the H3K27ac mark of androgen responsive genes (B) and luminal signature genes (C) is decreased in LNCaP/AR-ADORA2A cells upon CGS stimulation. (D) GSEA analysis displays the upregulated hallmarks in LNCaP/AR-ADORA2A cells upon CGS treatment based on the analysis of differential calling peaks of H3K27ac cut & tag experiments. (E) Cut & tag data demonstrate that luminal cell marker genes including AR, FKBP5, KRT8, and KRT18 promoters contain less H3K27ac marks in LNCaP/AR-ADORA2A cells in the presence of CGS. (F and G) Cut & tag results show that stem cell marker gene SOX2 (F) and NE-transcription factor gene MYCN (G) display increased H3K27ac modifications in LNCaP/AR-ADORA2A cells upon stimulation. (H) Motif analysis exhibits the most enriched transcription factor binding sites on H3K27ac peaks in LNCaP/AR-ADORA2A cells upon CGS stimulation.