Xiu Dianhui, Liu Lin, Cheng Min, Sun Xiaosong, Ma Xibo
Department of Radiology, China-Japan Union Hospital of Jilin University, Changchun 130021, Jilin, People's Republic of China.
Department of Thyroid-Head and Neck Surgery, Jilin Cancer Hospital, Changchun 130021, Jilin, People's Republic of China.
Onco Targets Ther. 2020 Mar 17;13:2319-2331. doi: 10.2147/OTT.S236860. eCollection 2020.
Prostate cancer (PCa) is a common malignant tumor of the urinary system in males. LncRNA taurine-upregulated gene 1 (TUG1) has been verified to play a crucial role in progression and prognosis of PCa. However, the functional mechanism of TUG1 remains unclear with radiosensitivity of PCa.
Quantitative real-time PCR (qRT-PCR) was conducted to measure the transcription levels of genes. 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay and flow cytometry analysis were employed to assess cell proliferation and apoptosis, respectively. Moreover, colony formation assay was used to measure colony survival. Western blot was performed to detect the relative proteins expression. The interaction among variables was predicted by online tool starbase, and then confirmed using the dual luciferase reporter assay. A xenograft mouse model was constructed to investigate the effect of TUG1 on tumor growth in vivo.
The levels of lncRNA TUG1 and SMC1A were remarkably increased, while miR-139-5p was downregulated in PCa. Patients with high expression of TUG1 showed a lower survival rate and poor prognosis. Knockdown of TUG1 inhibited PCa cell proliferation and colony survival fraction, and promoted apoptosis. Downregulation of miR-139-5p reversed the effects of TUG1 deletion on proliferation, apoptosis and colony survival fraction in PCa cells treated with 4 Gy of X-ray radiation. Moreover, TUG1 sponged miR-139-5p to regulate SMC1A expression. SMC1A deletion blocked the effects of TUG1 on the progression of PCa cells treated with 4 Gy of X-ray radiation. The tumor volume and weight were illustriously reduced with radiation and TUG1 silencing in xenograft model.
Knockdown of lncRNA TUG1 enhanced radiosensitivity in PCa via the TUG1/miR-139-5p/SMC1A axis. It may become a promising target for PCa treatment.
前列腺癌（PCa）是男性泌尿系统常见的恶性肿瘤。长链非编码RNA牛磺酸上调基因1（TUG1）已被证实对PCa的进展和预后起着关键作用。然而，TUG1在PCa放射敏感性方面的功能机制仍不清楚。
采用定量实时聚合酶链反应（qRT-PCR）检测基因转录水平。分别采用3-(4,5-二甲基噻唑-2)-2,5-二苯基四氮唑溴盐（MTT）法和流式细胞术分析评估细胞增殖和凋亡。此外，采用集落形成试验检测集落存活率。进行蛋白质免疫印迹法检测相关蛋白表达。通过在线工具starbase预测变量之间的相互作用，然后使用双荧光素酶报告基因试验进行验证。构建异种移植小鼠模型以研究TUG1对体内肿瘤生长的影响。
lncRNA TUG1和SMC1A水平在PCa中显著升高，而miR-139-5p下调。TUG1高表达的患者生存率较低且预后较差。敲低TUG1可抑制PCa细胞增殖和集落存活率，并促进细胞凋亡。miR-139-5p的下调逆转了TUG1缺失对接受4 Gy X射线辐射的PCa细胞增殖、凋亡和集落存活率的影响。此外，TUG1吸附miR-139-5p以调节SMC1A表达。SMC1A缺失阻断了TUG1对接受4 Gy X射线辐射的PCa细胞进展的影响。在异种移植模型中，辐射和TUG1沉默显著降低了肿瘤体积和重量。
敲低lncRNA TUG1通过TUG1/miR-139-5p/SMC1A轴增强PCa的放射敏感性。它可能成为PCa治疗的一个有前景的靶点。
