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长链非编码RNA TUG1与miR-145之间的双负反馈环促进人膀胱癌细胞的上皮-间质转化和放射抗性。

Double-negative feedback loop between long non-coding RNA TUG1 and miR-145 promotes epithelial to mesenchymal transition and radioresistance in human bladder cancer cells.

作者信息

Tan Jiemei, Qiu Kaifeng, Li Mingyi, Liang Ying

机构信息

Department of Oncology, Jiangmen Central Hospital, Affiliated Jiangmen Hospital of Sun Yat-sen, Jiangmen, China.

Department of pharmacy, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.

出版信息

FEBS Lett. 2015 Oct 7;589(20 Pt B):3175-81. doi: 10.1016/j.febslet.2015.08.020. Epub 2015 Aug 28.

DOI:10.1016/j.febslet.2015.08.020
PMID:26318860
Abstract

LncRNAs have a critical role in the regulation of cellular processes such as cancer progression and metastasis. In the present study, we confirmed that TUG1 was overexpressed in bladder cancer tissues and established cell lines. Knockdown of TUG1 inhibited bladder cancer cell metastasis both in vitro and in vivo. Furthermore, we found that TUG1 promoted cancer cell invasion and radioresistance through inducing epithelial-to-mesenchymal transition (EMT). Interestingly, TUG1 decreased the expression of miR-145 and there was a reciprocal repression between TUG1 and miR-145 in an Argonaute2-dependent manner. ZEB2 was identified as a down-stream target of miR-145 and TUG1 exerted its function through the miR-145/ZEB2 axis. In summary, our data indicated that blocking TUG1 function may be an effective anti-cancer therapy.

摘要

长链非编码RNA(LncRNAs)在调控细胞过程(如癌症进展和转移)中发挥着关键作用。在本研究中,我们证实了TUG1在膀胱癌组织和建立的细胞系中过表达。敲低TUG1在体外和体内均抑制了膀胱癌细胞转移。此外,我们发现TUG1通过诱导上皮-间质转化(EMT)促进癌细胞侵袭和放射抗性。有趣的是,TUG1降低了miR-145的表达,并且TUG1与miR-145之间以AGO2依赖的方式存在相互抑制。ZEB2被鉴定为miR-145的下游靶点,TUG1通过miR-145/ZEB2轴发挥其功能。总之,我们的数据表明阻断TUG1功能可能是一种有效的抗癌治疗方法。

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