Long non-coding RNA TUG1 promotes cell proliferation and metastasis by negatively regulating miR-300 in gallbladder carcinoma

被引:67
作者
Ma, Fei [1 ]
Wang, Shou-hua [2 ]
Cai, Qiang [2 ]
Jin, Long-yang [2 ]
Zhou, Di [2 ]
Ding, Jun [3 ]
Quan, Zhi-wei [2 ]
机构
[1] Shanghai Jiao Tong Univ, Xinhua Hosp, Dept Oncol, Sch Med, Shanghai 200092, Peoples R China
[2] Shanghai Jiao Tong Univ, Xinhua Hosp, Dept Gen Surg, Sch Med, 1665 Kongjiang Rd, Shanghai 200092, Peoples R China
[3] Shanghai Univ TCM, Shanghai Shuguang Hosp, Dept Biliary & Pancreat Surg, 528 Zhangheng Rd, Shanghai 201203, Peoples R China
关键词
Long non-coding RNA; TUG1; Proliferation; Metastasis; miR-300; Gallbladder carcinoma; MESENCHYMAL TRANSITION; DOWN-REGULATION; POOR-PROGNOSIS; GASTRIC-CANCER; UP-REGULATION; APOPTOSIS; GROWTH; TUMOR; EXPRESSION;
D O I
10.1016/j.biopha.2017.01.150
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Background: As we all know, long non-coding RNAs (lncRNAs) have been reported to play vital roles in various human cancers. In this study, we aimed to explore the role of lncRNA TUG1 in gallbladder carcinoma (GBC) development. Methods: Total RNA was extracted from the tissues of thirty GBC patients, four GBC cell lines. We detected the expression levels of TUG1 using quantitative real-time PCR. We performed CCK8, colony formation, transwell invasion and apoptosis assays to study the effects of TUG1 on GBC cell proliferation and invasion. Western blot assay was performed to assess to the expression level of epithelial-mesenchymal transition (EMT) markers in transforming growth factor-beta 1 (TGF-beta 1) treated and TUG1 knockdown GBC cell. Lastly, dual-luciferase reporter assay and quantitative real-time PCR were performed to verify the potential target microRNAs (miRNAs) of TUG1. Results: TUG1 expression was significantly overexpressed in GBC tissues. Functionally, this study demonstrated that knockdown of TUG1 significantly inhibited GBC cell proliferation, metastasis. Mechanically, we found that TUG1 is upregulated by TGF-beta 1, and knockdown of TUG1 inhibited GBC cell EMT. Furthermore, we identified that miR-300, which has been reported as a suppressor in other types of cancer, is negatively regulated by TUG1. Conclusions: LncRNA TUG1 promotes GBC cell proliferation, metastasis and EMT progression by functioning as a miRNA sponge to abrogate the endogenous effect of miR-300. (C) 2017 Elsevier Masson SAS. All rights reserved.
引用
收藏
页码:863 / 869
页数:7
相关论文
共 31 条
[1]   The functions of animal microRNAs [J].
Ambros, V .
NATURE, 2004, 431 (7006) :350-355
[2]  
[Anonymous], ONCOGENE
[3]  
[Anonymous], ONCOGENE
[4]  
Cai Q, 2016, AM J TRANSL RES, V8, P4068
[5]   Origins and Mechanisms of miRNAs and siRNAs [J].
Carthew, Richard W. ;
Sontheimer, Erik J. .
CELL, 2009, 136 (04) :642-655
[6]   Targeting long non-coding RNA-TUG1 inhibits tumor growth and angiogenesis in hepatoblastoma [J].
Dong, R. ;
Liu, G-B ;
Liu, B-H ;
Chen, G. ;
Li, K. ;
Zheng, S. ;
Dong, K-R .
CELL DEATH & DISEASE, 2016, 7 :e2278-e2278
[7]  
Ge WS, 2016, AM J TRANSL RES, V8, P3903
[8]   ADJUVANT THERAPY FOR GALLBLADDER CARCINOMA: THE MAYO CLINIC EXPERIENCE [J].
Gold, Douglas G. ;
Miller, Robert C. ;
Haddock, Michael G. ;
Gunderson, Leonard L. ;
Quevedo, Fernando ;
Donohue, John H. ;
Bhatia, Sumita ;
Nagorney, David M. .
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 2009, 75 (01) :150-155
[9]   Long non-coding RNA TUG1 is up-regulated in hepatocellular carcinoma and promotes cell growth and apoptosis by epigenetically silencing of KLF2 [J].
Huang, Ming-De ;
Chen, Wen-Ming ;
Qi, Fu-Zhen ;
Sun, Ming ;
Xu, Tong-Peng ;
Ma, Pei ;
Shu, Yong-qian .
MOLECULAR CANCER, 2015, 14
[10]   A Cytoplasmic NF-κB Interacting Long Noncoding RNA Blocks IκB Phosphorylation and Suppresses Breast Cancer Metastasis [J].
Liu, Bodu ;
Sun, Lijuan ;
Liu, Qiang ;
Gong, Chang ;
Yao, Yandan ;
Lv, Xiaobin ;
Lin, Ling ;
Yao, Herui ;
Su, Fengxi ;
Li, Dangsheng ;
Zeng, Musheng ;
Song, Erwei .
CANCER CELL, 2015, 27 (03) :370-381