Fig. 4: CBP/p300 acts in concert to alter the global transcriptome in PCa cells and regulate DDR.

A 22Rv1- shCON, shCBP, and shP300 cells were treated with doxycycline to induce knockdown, and RNA Seq analysis was performed in quadruplet samples. MA plot depicts gene expression modulation with the number of significant upregulated and downregulated transcripts with p < 0.001 and fold change (FC) > 2.0. B GSEA of RNA-Seq (KEGG Pathways) identified deenriched pathways with CBP and p300 knockdown treatment in 22Rv1 cells using FDR < 0.25. C–E. 22Rv1-shCON, -shCBP, and –shp300 cells were treated with doxycycline and 5 Gy IR. C Flow analysis was performed to determine changes in cell cycle progression. Cells were harvested, and mRNA (D) was isolated. Changes in c-MYC, TP53, and CDKN1A (p21) and 18S mRNA expression. E 22Rv1-shCON, -shCBP, and –shp300 cells were treated with doxycycline to knockdown CBP and p300. Cells were also treated with IR (5 Gy) at Day 1. Cells were harvested for growth assays analyses on Days 1, 3, and 5 using Picogreen. F 22Rv1 (top) and C4-2 (bottom) cells were treated with increasing dosages of indicated DDR agents (Doxorubicin, Cisplatin, or Olaparib), and drug sensitivity assays were performed on Day 5 using Picogreen. G Non-linear regression analyses were performed to determine the IC₅₀ values. n = 3, *p < 0.05, **p < 0.01, and ***p < 0.001.