A CRISPR Interference of CBP and p300 Selectively Induced Synthetic Lethality in Bladder Cancer Cells In Vitro

The transcriptional coactivator CREB-binding protein (CBP) and p300 are adenoviral E1A-binding proteins involved in various cellular processes, including embryonic development, homeostasis, cell differentiation and transcription activation. Previous study suggested that synthetic lethality between CBP and p300 inhibition in lung and hematopoietic cancers. However, the underlying mechanism of CBP and p300 paralog in bladder cancer remains unknown. In this study, we discovered that combined CBP and p300 inhibition impaired cell proliferation and induced apoptosis of bladder cancer cells and normal bladder urothelial cell via decreasing c-Myc expression. Then, we employed the dCas9-KRAB system, hTERT promoter and hUPII promoter to construct an CRISPR interference system which could specifically repress CBP and p300 expression and cause lethality in bladder cancer cells in vitro. The CRISPR interference system we constructed could specifically inhibit the progression of bladder cancer, providing a novel strategy to fight against bladder cancer.