A Light-Inducible Split-dCas9 System for Inhibiting the Progression of Bladder Cancer Cells by Activating p53 and E-cadherin

Xinbo Huang; Qun Zhou; Mingxia Wang; Congcong Cao; Qian Ma; Jing Ye; Yaoting Gui

doi:10.3389/fmolb.2020.627848

A Light-Inducible Split-dCas9 System for Inhibiting the Progression of Bladder Cancer Cells by Activating p53 and E-cadherin

Front Mol Biosci. 2021 Jan 5:7:627848. doi: 10.3389/fmolb.2020.627848. eCollection 2020.

Authors

Xinbo Huang¹, Qun Zhou², Mingxia Wang¹, Congcong Cao¹, Qian Ma¹, Jing Ye¹, Yaoting Gui¹

Affiliations

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, China.
² Department of Urology, The Affiliated Nanhua Hospital of University of South China, Hengyang, China.

Abstract

Optogenetic systems have been increasingly investigated in the field of biomedicine. Previous studies had found the inhibitory effect of the light-inducible genetic circuits on cancer cell growth. In our study, we applied an AND logic gates to the light-inducible genetic circuits to inhibit the cancer cells more specifically. The circuit would only be activated in the presence of both the human telomerase reverse transcriptase (hTERT) and the human uroplakin II (hUPII) promoter. The activated logic gate led to the expression of the p53 or E-cadherin protein, which could inhibit the biological function of tumor cells. In addition, we split the dCas9 protein to reduce the size of the synthetic circuit compared to the full-length dCas9. This light-inducible system provides a potential therapeutic strategy for future bladder cancer.

Keywords: CRISPR; bladder cancer; light-inducible; logic gate; split-dCas9.