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

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.

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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