A CRISPR Interference of CBP and p300 Selectively Induced Synthetic Lethality in Bladder Cancer Cells In Vitro
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Updated: Jan 23, 2026

Dual CRISPR-Interference Strategy for Targeting Synthetic Lethal Interactions Between Non-Coding RNAs in Cancer Cells
Published on: May 30, 2025
Jianfa Li1, ChenChen Huang1,2, Tiefu Xiong1
1Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Institute of Urology, Peking University Shenzhen Hospital, Shenzhen-Peking University-the Hong Kong University of Science and Technology Medical Center, Shenzhen 518000, People's Republic of China.
Abstract:
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.
Insights
Combined inhibition of CREB-binding protein (CBP) and p300 impairs bladder cancer cell growth by reducing c-Myc. A novel CRISPR interference system specifically targets CBP and p300 for bladder cancer treatment.
Area of Science:
- Molecular Biology
- Cancer Research
- Epigenetics
Background:
- CREB-binding protein (CBP) and p300 are transcriptional coactivators crucial for cellular processes.
- Synthetic lethality of CBP/p300 inhibition is known in lung and hematopoietic cancers.
- The role of CBP and p300 in bladder cancer remains unclear.
Purpose of the Study:
- To investigate the mechanism of CBP and p300 paralogs in bladder cancer.
- To explore the therapeutic potential of combined CBP and p300 inhibition.
- To develop a novel CRISPR interference system for bladder cancer treatment.
Main Methods:
- Combined inhibition of CBP and p300 in bladder cancer cells.
- Analysis of c-Myc expression levels.
- Construction of a CRISPR interference system using dCas9-KRAB, hTERT, and hUPII promoters.
Main Results:
- Combined CBP and p300 inhibition reduced proliferation and induced apoptosis in bladder cancer cells.
- This effect was mediated by decreased c-Myc expression.
- The developed CRISPR interference system specifically repressed CBP and p300, causing lethality in bladder cancer cells in vitro.
Conclusions:
- Combined CBP and p300 inhibition represents a potential therapeutic strategy for bladder cancer.
- Targeting CBP and p300 via CRISPR interference offers a novel approach to specifically inhibit bladder cancer progression.
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