Int J Biol Sci 2019; 15(6):1276-1286. doi:10.7150/ijbs.32332

Research Paper

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

Jianfa Li1*, ChenChen Huang1,2*, Tiefu Xiong1, Changshui Zhuang1, Chengle Zhuang1, Yawen Li1,2, Jing Ye1✉, Yaoting Gui1✉

1. Guangdong 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
2. Anhui Medical University, Hefei 230000, Anhui Province, People's Republic of China
*These authors have contributed equally to this work.

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Citation:
Li J, Huang C, Xiong T, Zhuang C, Zhuang C, Li Y, Ye J, Gui Y. A CRISPR Interference of CBP and p300 Selectively Induced Synthetic Lethality in Bladder Cancer Cells In Vitro. Int J Biol Sci 2019; 15(6):1276-1286. doi:10.7150/ijbs.32332. Available from http://www.ijbs.com/v15p1276.htm

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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.

Keywords: bladder cancer, CBP, p300, synthetic lethality, CRISPR interference system