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长链非编码RNA PVT1通过介导微小RNA-186靶向Twist1促进前列腺癌的上皮-间质转化。

Long noncoding RNA PVT1 promotes EMT via mediating microRNA-186 targeting of Twist1 in prostate cancer.

作者信息

Chang Zhongwen, Cui Jun, Song Yongsheng

机构信息

Department of Urology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, PR China.

Department of Urology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, PR China.

出版信息

Gene. 2018 May 15;654:36-42. doi: 10.1016/j.gene.2018.02.036. Epub 2018 Feb 13.

Abstract

The pathogenesis and the underlying mechanism of endothelial-mesenchymal transition in prostate cancer remain unclear. Plasmacytoma variant translocation 1 (PVT1), a novel long non-coding RNA maps to 8q24.21, and in many tumor studies the up-regulation of PVT1 has already been reported. PVT1 is closely related to tumor cell proliferation, invasion, and metastasis. In this study, we employed a combination of techniques to study the role of PVT1 in prostate cancer, which included bioinformatic analysis, Western blotting and cell migration assays of prostate cancer cell lines. We report that PVT1 promotes prostate cancer invasion and metastasis by modulating EMT. Furthermore, PVT1 can promote EMT by up-regulation of Twist1, a transcription factor associated with EMT. We then confirmed that PVT1 acts as a sponge for miRNA-186-5p and positively regulates Twist1 by a sponge effect. Therefore, this study has revealed a novel MECHANISM for the promotion of EMT in prostate cancer by PVT1. Our findings suggest that the PVT1/miR-186/Twist1 regulatory axis may be a new therapeutic target for prostate cancer.

摘要

前列腺癌中内皮-间充质转化的发病机制及潜在机制仍不清楚。浆细胞瘤变异易位1(PVT1)是一种定位于8q24.21的新型长链非编码RNA,在许多肿瘤研究中已报道PVT1上调。PVT1与肿瘤细胞增殖、侵袭和转移密切相关。在本研究中,我们采用多种技术研究PVT1在前列腺癌中的作用,包括生物信息学分析、蛋白质印迹法以及前列腺癌细胞系的细胞迁移实验。我们报告PVT1通过调节上皮-间充质转化(EMT)促进前列腺癌侵袭和转移。此外,PVT1可通过上调与EMT相关的转录因子Twist1来促进EMT。然后我们证实PVT1作为miRNA-186-5p的海绵,并通过海绵效应正向调节Twist1。因此,本研究揭示了PVT1促进前列腺癌EMT的一种新机制。我们的研究结果表明,PVT1/miR-186/Twist1调控轴可能是前列腺癌的一个新治疗靶点。

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