title: Long non-coding RNA-LET is a positive prognostic factor and exhibits tumor-suppressive activity in gallbladder cancer.
abstract: 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.
authors.affiliation: Department of General Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.|Department of General Surgery, Taixing people's Hospital, Yangzhou University School of Medicine, Jiangsu Province, China.
authors.forename: Ming-zhe
authors.initials: MZ
authors.lastname: Ma
authors.affiliation: Department of Endocrinology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.|Department of Pharmacology, Wannan Medical College, Anhui, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Kong
authors.affiliation: Department of General Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Ming-zhe
authors.initials: MZ
authors.lastname: Weng
authors.affiliation: Department of General Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Ming-di
authors.initials: MD
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Yi-yu
authors.initials: YY
authors.lastname: Qin
authors.affiliation: Department of General Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Gong
authors.affiliation: Department of General Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Wen-jie
authors.initials: WJ
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Zhi-wei
authors.initials: ZW
authors.lastname: Quan
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D014408:Biomarkers, Tumor / Q000235:genetics; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints / Q000235:genetics; D005706:Gallbladder Neoplasms / Q000235:genetics* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D011379:Prognosis; D062085:RNA, Long Noncoding / Q000235:genetics*; D016192:Resting Phase, Cell Cycle / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D062085:RNA, Long Noncoding
keywords: gallbladder cancer; hypoxia; lncRNA-LET; long non-coding RNA; prognosis