The prognostic potential and carcinogenesis of long non-coding RNA TUG1 in human cholangiocarcinoma.

Yi Xu,Zhenglong Li,Fumin Zhang,Kaiming Leng,Pengcheng Kang,Xiangyu Zhong,Xingming Jiang,Yunfu Cui

doi:10.18632/oncotarget.19502

Yi Xu, Zhenglong Li + Show 6 more

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https://doi.org/10.18632/oncotarget.19502

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Abstract

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 (p=0.005), TNM stage (p=0.013), postoperative recurrence (p=0.036) and overall survival (p=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 in vitro by reversing EMT. Overall, our results suggest that TUG1 may be a rational CCA-related prognostic factor and therapeutic target.

Highlights

Cholangiocarcinoma (CCA) is a carcinoma derived from neoplastic transformation of biliary epithelial cells located in the intrahepatic and extrahepatic bile ducts
The majority of cell lines showed substantially higher levels of taurineup-regulated gene 1 (TUG1) expression compared to Human intrahepatic biliary epithelial cells (HIBEC) cells, indicating that TUG1 might be involved in tumorigenesis and progression of CCA (Huh28, p=0.038; KMBC, p=0.033; HuCCT1, p=0.003; QBC939, p
TUG1 overexpression is correlated with poor prognosis in CCA patients

Summary

Introduction

Cholangiocarcinoma (CCA) is a carcinoma derived from neoplastic transformation of biliary epithelial cells located in the intrahepatic and extrahepatic bile ducts. It is the second most common primary liver malignant tumor after hepatocellular carcinoma (HCC) and the most common biliary tract malignancy worldwide [1, 2]. CCA is a deadly carcinoma with poor prognosis worldwide and is characterized by its resistance to conventional chemotherapy and radiotherapy, in addition to a lack of available methods for early diagnosis and treatment [4, 5]. Surgery is only possible in a significant minority of patients who present at an early stage and the 5-year survival rate of CCA is only 10% [7]. The precise mechanism associated with malignant pathogenesis and progression of CCA remains unclear

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