Xu Yi, Leng Kaiming, Li Zhenglong, Zhang Fumin, Zhong Xiangyu, Kang Pengcheng, Jiang Xingming, Cui Yunfu
Department of Hepatopancreatobiliary Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, China.
Department of The Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry of Education, Harbin, China.
Oncotarget. 2017 Jul 22;8(39):65823-65835. doi: 10.18632/oncotarget.19502. eCollection 2017 Sep 12.
Cholangiocarcinoma (CCA) is a fatal disease with increasing worldwide incidence and is characterized by poor prognosis due to its poor response to conventional chemotherapy or radiotherapy. Long non-coding RNAs (lncRNAs) play key roles in multiple human cancers, including CCA. Cancer progression related lncRNA taurine-up-regulated gene 1 (TUG1) was reported to be involved in human carcinomas. However, the impact of TUG1 in CCA is unclear. The aim of this study was to explore the expression pattern of TUG1 and evaluate its clinical significance as well as prognostic potential in CCA. In addition, the functional roles of TUG1 including cell proliferation, apoptosis, migration, invasion and epithelial-mesenchymal transition (EMT), were evaluated after TUG1 silencing. Our data demonstrated up-regulation of TUG1 in both CCA tissues and cell lines. Moreover, overexpression of TUG1 is linked to tumor size (=0.005), TNM stage (=0.013), postoperative recurrence (=0.036) and overall survival (=0.010) of CCA patients. Furthermore, down-regulation of TUG1 following RNA silencing reduced cell growth and increased apoptosis in CCA cells. Additionally, TUG1 suppression inhibited metastasis potential by reversing EMT. Overall, our results suggest that TUG1 may be a rational CCA-related prognostic factor and therapeutic target.
胆管癌(CCA)是一种全球发病率不断上升的致命疾病,其特点是对传统化疗或放疗反应不佳,预后较差。长链非编码RNA(lncRNA)在包括CCA在内的多种人类癌症中发挥关键作用。据报道,与癌症进展相关的lncRNA牛磺酸上调基因1(TUG1)参与人类癌症。然而,TUG1在CCA中的影响尚不清楚。本研究的目的是探讨TUG1的表达模式,评估其在CCA中的临床意义以及预后潜力。此外,在沉默TUG1后,评估了TUG1在细胞增殖、凋亡、迁移、侵袭和上皮-间质转化(EMT)等方面的功能作用。我们的数据表明,TUG1在CCA组织和细胞系中均上调。此外,TUG1的过表达与CCA患者的肿瘤大小(=0.005)、TNM分期(=0.013)、术后复发(=0.036)和总生存期(=0.010)相关。此外,RNA沉默后TUG1的下调降低了CCA细胞的生长并增加了细胞凋亡。此外,TUG1的抑制通过逆转EMT抑制了转移潜能。总体而言,我们的结果表明,TUG1可能是一个合理的与CCA相关的预后因素和治疗靶点。