Oncotarget

Research Papers:

Long noncoding RNA TUG1 is a diagnostic factor in lung adenocarcinoma and suppresses apoptosis via epigenetic silencing of BAX

Huan Liu, Guizhi Zhou _, Xin Fu, Haiyan Cui, Guangrui Pu, Yao Xiao, Wei Sun, Xinhua Dong, Libin Zhang, Sijia Cao, Guiqin Li, Xiaowei Wu and Xu Yang

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Oncotarget. 2017; 8:101899-101910. https://doi.org/10.18632/oncotarget.22058

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Abstract

Huan Liu1, Guizhi Zhou1, Xin Fu1, Haiyan Cui1, Guangrui Pu1, Yao Xiao1, Wei Sun1, Xinhua Dong1, Libin Zhang1, Sijia Cao1, Guiqin Li1, Xiaowei Wu1 and Xu Yang1

1Health Physical Examination Department of The Third Department, The First Affiliated hospital of Dalian Medical University, Dalian, Liaoning, China

Correspondence to:

Guizhi Zhou, email: dytjbzgz@163.com

Keywords: lung adenocarcinoma, lncRNA TUG1, BAX, EZH2, diagnosis

Received: August 31, 2017     Accepted: September 20, 2017     Published: October 19, 2017

ABSTRACT

Lung cancer is one of the leading causes of cancer-related mortality, and responds badly to existing treatment. Thus, it is of urgent need to identify novel diagnostic markers and therapeutic targets. Increasing evidences have indicated that long non-coding RNAs (lncRNAs) play an important role in initiation and progression of lung cancer. However, the role of lncRNA Taurine upregulated 1 (TUG1) in lung adenocarcinoma (LAD) progression is not well known. In this study, we determined the diagnostic value of TUG1 in LAD patients, and further uncovered the underlying functional mechanism. Our results showed that TUG1 was significantly upregulated in LAD cells and serum samples. Receiver operator characteristic (ROC) analysis suggested a relatively higher area under the curve (AUC) of TUG1 (0.756) contrast to cyfra21-1 (0.619). In addition, high TUG1 level was associated with enhanced tumor size, degree of differentiation, lymph node metastases, distant metastasis and TNM stage. Cell functional assays showed that knockdown of TUG1 suppressed LAD cell viability and promoted cell apoptosis. We then sought to reveal the underlying regulatory mechanism, and the pro-apoptotic protein BAX was then identified as the downstream target of TUG1. Gain and loss functional assays showed that inhibition of BAX reversed the induced apoptosis by TUG1 knockdown. Finally, RNA immunoprecipitation and Chromatin immunoprecipitation revealed that TUG1 suppressed BAX expression through physically interacting with EZH2. In conclusion, lncRNA TUG1 is a promising diagnostic marker for LAD patients and suppression of TUG1 levels could be a future direction to promote the prognosis of LAD patients.


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