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A Light-Inducible Split-dCas9 System for Inhibiting the Progression of Bladder Cancer Cells by Activating p53 and E-cadherin
Frontiers in Molecular Biosciences ( IF 5 ) Pub Date : 2020-12-02 , DOI: 10.3389/fmolb.2020.627848
Xinbo Huang , Qun Zhou , Mingxia Wang , Congcong Cao , Qian Ma , Jing Ye , Yaoting Gui

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.



中文翻译:

光激活split-dCas9系统,通过激活p53和E-cadherin抑制膀胱癌细胞的进程

在生物医学领域,光遗传学系统已得到越来越多的研究。先前的研究已经发现了光诱导性遗传电路对癌细胞生长的抑制作用。在我们的研究中,我们将“与”逻辑门应用于可光诱导的遗传电路,以更具体地抑制癌细胞。仅在存在人类端粒酶逆转录酶(hTERT)和人类uroplakin II(hUPII)启动子的情况下才激活该电路。激活的逻辑门导致p53或E-cadherin蛋白的表达,这可能抑制肿瘤细胞的生物学功能。此外,与全长dCas9相比,我们拆分了dCas9蛋白以减小合成电路的大小。这种光诱导系统为将来的膀胱癌提供了潜在的治疗策略。

更新日期:2021-01-05
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