长链非编码 RNA TUG1 通过调控 miR-128-3p/YES1 轴促进前列腺癌进展。
Long non-coding TUG1 accelerates prostate cancer progression through regulating miR-128-3p/YES1 axis.
机构信息
Department of Urology, Zhejiang Integrated Traditional and Western Medicine Hospital/Hangzhou Red Cross Hospital, Hangzhou, China.
出版信息
Eur Rev Med Pharmacol Sci. 2020 Jan;24(2):619-632. doi: 10.26355/eurrev_202001_20038.
OBJECTIVE
Dysregulation of long non-coding RNAs (lncRNAs) is being found to have relevance to human cancers, including prostate cancer (PCa). Taurine-upregulated gene 1 (TUG1) has been demonstrated to have a potential oncogenic role in PCa. Then the aim of this study was to investigate the molecular mechanisms of TUG1 on PCa progression.
PATIENTS AND METHODS
The expression levels of TUG1, YES proto-oncogene 1 (YES1) mRNA and miR-128-3p were assessed using quantitative real-time polymerase chain reaction. Cell proliferation ability, apoptosis, and migration and invasion capacities were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, flow cytometry and transwell assay, respectively. Western blot analysis was employed to evaluate the indicated proteins levels. The interaction between miR-128-3p and TUG1 or YES1 was determined using the Dual-Luciferase reporter assay. In vivo assay was used to observe the effect of TUG1 on tumor growth in vivo.
RESULTS
Our data indicated that TUG1 was upregulated in PCa tissues and cells and predicted poor prognosis. TUG1 knockdown weakened PCa cell proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), and accelerated cell apoptosis in vitro. Mechanistically, TUG1 directly interacted with miR-128-3p and miR-128-3p mediated the regulatory effects of TUG1 depletion on PCa cell progression. YES1 was a direct target of miR-128-3p and TUG1 modulated YES1 expression by sponging miR-128-3p. Moreover, TUG1 silencing repressed PCa cell progression in vitro through YES1. Additionally, TUG1 silencing mitigated tumor growth in vivo.
CONCLUSIONS
Our study suggested that TUG1 silencing retarded PCa cell progression in vitro and tumor growth in vivo through miR-128-3p/YES1 axis, showing that targeting TUG1 might be a novel therapeutic strategy for PCa management.
目的
长链非编码 RNA（lncRNA）的失调被发现与人类癌症有关，包括前列腺癌（PCa）。牛磺酸上调基因 1（TUG1）已被证明在 PCa 中具有潜在的致癌作用。因此，本研究旨在探讨 TUG1 对 PCa 进展的分子机制。
患者和方法
采用实时定量聚合酶链反应检测 TUG1、YES 原癌基因 1（YES1）mRNA 和 miR-128-3p 的表达水平。通过 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基-2H-四唑溴盐（MTT）测定、流式细胞术和 Transwell 测定分别检测细胞增殖能力、细胞凋亡以及迁移和侵袭能力。Western blot 分析用于评估指示蛋白的水平。采用双荧光素酶报告基因测定法确定 miR-128-3p 与 TUG1 或 YES1 之间的相互作用。体内实验用于观察 TUG1 对体内肿瘤生长的影响。
结果
我们的数据表明，TUG1 在 PCa 组织和细胞中上调，并预测预后不良。TUG1 敲低削弱了 PCa 细胞的增殖、迁移、侵袭、上皮间质转化（EMT），并加速了细胞凋亡。在体外。机制上，TUG1 直接与 miR-128-3p 相互作用，miR-128-3p 介导 TUG1 耗竭对 PCa 细胞进展的调节作用。YES1 是 miR-128-3p 的直接靶标，TUG1 通过海绵 miR-128-3p 调节 YES1 的表达。此外，TUG1 沉默通过 YES1 在体外抑制 PCa 细胞的进展。此外，TUG1 沉默减轻了体内肿瘤的生长。
结论
本研究表明，TUG1 沉默通过 miR-128-3p/YES1 轴在体外抑制 PCa 细胞的进展和体内肿瘤的生长，表明靶向 TUG1 可能是 PCa 管理的一种新的治疗策略。
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