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学科主题: 临床医学
题名:
Synthesizing oncogenic signal-processing systems that function as both "signal counters′′ and "signal blockers′′ in cancer cells
作者: Liu, Yuchen1,2,3; Huang, Weiren1,3; Zhou, Dexi2; Han, Yonghua1,3; Duan, Yonggang1,3; Zhang, Xiaoyue1,2,3; Zhang, Hu2,3; Jiang, Zhimao3; Gui, Yaoting3; Cai, Zhiming1,3
刊名: MOLECULAR BIOSYSTEMS
发表日期: 2013
DOI: 10.1039/c3mb70093c
卷: 9, 期:7, 页:1909-1918
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Biochemistry & Molecular Biology
研究领域[WOS]: Biochemistry & Molecular Biology
关键词[WOS]: FACTOR-KAPPA-B ; SYNTHETIC BIOLOGY ; GENE NETWORKS ; BETA-CATENIN ; TRANSLATION ; EXPRESSION ; PROTEIN ; QUADRUPLEXES ; INTEGRATOR ; ACTIVATION
英文摘要:

RNA-protein interaction plays a significant role in regulating eukaryotic translation. This phenomenon raises questions about the ability of artificial biological systems to take the advantage of protein-RNA interaction. Here, we designed an oncogenic signal-processing system expressing both a Renilla luciferase reporter gene controlled by RNA-protein interaction in its 50-untranslated region (5′-UTR) and a Firefly luciferase normalization gene. To test the ability of the designed system, we then constructed vectors targeting the nuclear factor-kappa B (NF-kappa B) or the beta-catenin signal. We found that the inhibition (%) of luciferase expression was correlated to the targeted protein content, allowing quantitative measurement of oncogenic signal intensity in cancer cells. The systems inhibited the expression of oncogenic signal downstream genes and induced bladder cancer cell proliferation inhibition and apoptosis without affecting normal urothelial cells. Compared to traditional methods (ELISA and quantitative immunoblotting), the bio-systems provided highly accurate, consistent, and reproducible quantification of protein signals and were able to discriminate between cancerous and non-cancerous cells. In conclusion, the synthetic systems function as both "signal counters′′ and "signal blockers′′ in cancer cells. This approach provides a synthetic biology platform for oncogenic signal measurement and cancer treatment.

语种: 英语
所属项目编号: JCYJ20120614155650545 ; ZDSY20120615154448514 ; 2012AA02A208 ; 81100460 ; 20100001110100
项目资助者: Basic Research Program of Shenzhen ; promotion Program for Shenzhen Key Laboratory ; National High Technology Research and Development Program of China (863 Program) ; National Natural Science Foundation of China ; PhD Programs Foundation of Ministry of Education of China
WOS记录号: WOS:000319882200035
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/53933
Appears in Collections:北京大学深圳医院_期刊论文

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作者单位: 1.Anhui Med Univ, Hefei 230032, Peoples R China
2.Shenzhen Univ, Affiliated Hosp 1, Shenzhen Peoples Hosp 2, Shenzhen 518039, Peoples R China
3.Peking Univ, Shenzhen Hosp, Guangdong & Shenzhen Key Lab Male Reprod Med & Ge, Shenzhen PKU HKUST Med Ctr,Inst Urol, Shenzhen 518036, Peoples R China

Recommended Citation:
Liu, Yuchen,Huang, Weiren,Zhou, Dexi,et al. Synthesizing oncogenic signal-processing systems that function as both "signal counters′′ and "signal blockers′′ in cancer cells[J]. MOLECULAR BIOSYSTEMS,2013,9(7):1909-1918.
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