Theophylline controllable RNAi-based genetic switches regulate expression of lncRNA TINCR and malignant phenotypes in bladder cancer cells.
Theophylline controllable RNAi-based genetic switches regulate expression of lncRNA TINCR and malignant phenotypes in bladder cancer cells.
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DOI：
10.1038/srep30798
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发表时间：
2016-09-02
影响因子：
4.6
通讯作者：
Cai Z
中科院分区：
文献类型：
--
作者：
Chen Z;Liu Y;He A;Li J;Chen M;Zhan Y;Lin J;Zhuang C;Liu L;Zhao G;Huang W;Cai Z
TINCR是众所周知的lncRNA，其在体细胞分化发育中充当主调节因子。然而，目前还不清楚TINCR是否也参与癌症的发生和进展。在本研究中，我们观察到TINCR在膀胱癌组织和细胞中上调，并有助于肿瘤发生和癌症进展。TINCR基因沉默可抑制膀胱尿路上皮癌细胞增殖，促进细胞凋亡，提示TINCR基因可能成为膀胱尿路上皮癌潜在的治疗靶点。因此，我们使用合成生物学方法来创建茶碱可控的基于RNAi的基因开关，其以剂量依赖性方式沉默TINCR。RNAi-OFF和ON开关均可用于定量控制膀胱癌中TINCR的表达，以抑制膀胱癌的进展。提示lncRNA-TINCR可促进膀胱癌的发生发展，通过诱导型RNAi调控其表达可能成为治疗膀胱癌的一种新策略。
TINCR is a well-known lncRNA which acts as a master regulator in somatic differentiation development. However, it is still unclear whether TINCR is also involved in caner occurrence and progression. In this study, we observed that TINCR was up-regulated in bladder cancer tissues and cells and contributed to oncogenesis and cancer progression. Silencing TINCR expression inhibited cell proliferation and promoted apoptosis in vitro, indicating that TINCR may be the potential therapeutic target for treating bladder urothelial carcinoma. Thus we used the synthetic biology approach to create theophylline controllable RNAi-based genetic switches which silenced TINCR in a dosage-dependent manner. Both RNAi-OFF and ON switches can be used to quantitatively control the expression of TINCR in bladder cancer to suppress the progression of bladder cancer. These findings suggest that lncRNA-TINCR could promote bladder cancer development and progression and artificial control of its expression through inducible RNAi may represent a new kind of therapeutic strategy for treating human bladder cancer.
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DOI：
10.1073/pnas.1514383113
发表时间：
2016-02-02
影响因子：
11.1
作者：
Saxena，Pratik;Charpin-El Hamri，Ghislaine;Fussenegger，Martin
通讯作者：
Fussenegger，Martin
影响因子：
16.8
作者：
通讯作者：
--
DOI：
10.1016/j.urolonc.2015.06.003
发表时间：
2015-10-01
影响因子：
2.7
作者：
Li, Shi;Yu, Zhe;Tan, Wan-Long
通讯作者：
Tan, Wan-Long
影响因子：
2.1
作者：
ARIEL, I;LUSTIG, O;HOCHBERG, A
通讯作者：
HOCHBERG, A
影响因子：
16.6
作者：
Liu, Yuchen;Zeng, Yayue;Cai, Zhiming
通讯作者：
Cai, Zhiming