Long non-coding RNA-LET is a positive prognostic factor and exhibits tumor-suppressive activity in gallbladder cancer

• Published in: Molecular carcinogenesis 2015-11, Vol.54 (11), p.1397-1406
• Main Authors: Ma, Ming-zhe, Kong, Xiang, Weng, Ming-zhe, Zhang, Ming-di, Qin, Yi-yu, Gong, Wei, Zhang, Wen-jie, Quan, Zhi-wei
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis - genetics; Biomarkers, Tumor - genetics; Cancer; Cancer therapies; Cell Line, Tumor; Down-Regulation - genetics; Female; G1 Phase Cell Cycle Checkpoints - genetics; Gallbladder; gallbladder cancer; Gallbladder Neoplasms - genetics; Gallbladder Neoplasms - pathology; Gene Expression Regulation, Neoplastic - genetics; Humans; hypoxia; lncRNA-LET; long non-coding RNA; Male; Mice; Mice, Nude; Middle Aged; Molecular biology; Prognosis; Resting Phase, Cell Cycle - genetics; Ribonucleic acid; RNA; RNA, Long Noncoding - genetics
• ISSN: 0899-1987; 1098-2744
• DOI: 10.1002/mc.22215

The identification of cancer‐associated long non‐coding RNAs (lncRNAs) and the investigation of their molecular and biological functions are vital for understanding the molecular biology and progression of cancer. The lncRNA‐LET, a newly identified lncRNA, was demonstrated to be down‐regulated in hepatocellular cancer. However, little is known about its role in gallbladder cancer. In the present study, an obvious down‐regulation of lncRNA‐LET was observed in gallbladder cancer compared to their adjacent normal tissues. Meanwhile, patients with low expression of lncRNA‐LET have significantly poorer prognosis than those with high expression. We confirmed that hypoxia decreased lncRNA‐LET levels in gallbladder cancer cells. Moreover, lncRNA‐LET overexpression was further validated to inhibit the invasion of gallbladder cancer cells under hypoxic or normoxic conditions in vitro. We demonstrated that lncRNA‐LET overexpression conferred a proliferative advantage to tumor cells under hypoxic conditions. The ectopic expression of lncRNA‐LET led to the promotion of cell cycle arrest at G0/G1 phase and to the induction of apoptosis under hypoxic conditions. Ectopic expression of LncRNA‐LET also suppressed gallbladder tumor growth in vivo. Our findings indicate that lncRNA‐LET may represent a prognostic marker and a potential therapeutic target for gallbladder cancer. © 2014 Wiley Periodicals, Inc.