LncRNA-PAGBC acts as a microRNA sponge and promotes gallbladder tumorigenesis

• Published in: EMBO reports Vol. 18; no. 10; pp. 1837 - 1853
• Main Authors: Wu, Xiang-Song, Wang, Fang, Li, Huai-Feng, Hu, Yun-Ping, Jiang, Lin, Zhang, Fei, Li, Mao-Lan, Wang, Xu-An, Jin, Yun-Peng, Zhang, Yi-Jian, Lu, Wei, Wu, Wen-Guang, Shu, Yi-Jun, Weng, Hao, Cao, Yang, Bao, Run-Fa, Liang, Hai-Bin, Wang, Zheng, Zhang, Yi-Chi, Gong, Wei, Zheng, Lei, Sun, Shu-Han, Liu, Ying-Bin
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.10.2017; Blackwell Publishing Ltd; John Wiley and Sons Inc
• Subjects: AKT protein; Binding; Cancer; Carcinogenesis - genetics; Cell Line, Tumor; Cell Proliferation; Cell Transformation, Neoplastic; ceRNA; Functional analysis; Gallbladder; Gallbladder - physiopathology; Gallbladder cancer; Gallbladder Neoplasms - genetics; Gallbladder Neoplasms - pathology; Gene Expression Regulation, Neoplastic; Humans; lncRNA; Metastases; Metastasis; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; miRNA; Neoplasm Metastasis; PAGBC; Pathogenesis; Polyadenylation; Prognosis; Proto-Oncogene Proteins c-akt - metabolism; Ribonucleic acid; RNA; RNA Biology; RNA, Long Noncoding - genetics; Signal Transduction; TOR protein; TOR Serine-Threonine Kinases - metabolism; Tumorigenesis; Tumors; ceRNA; gallbladder cancer; PAGBC; lncRNA; prognosis
• ISSN: 1469-221X; 1469-3178; 1469-3178
• DOI: 10.15252/embr.201744147

Long noncoding RNAs (lncRNAs) play roles in the development and progression of many cancers; however, the contributions of lncRNAs to human gallbladder cancer (GBC) remain largely unknown. In this study, we identify a group of differentially expressed lncRNAs in human GBC tissues, including prognosis-associated gallbladder cancer lncRNA (lncRNA-PAGBC), which we find to be an independent prognostic marker in GBC. Functional analysis indicates that lncRNA-PAGBC promotes tumour growth and metastasis of GBC cells. More importantly, as a competitive endogenous RNA (ceRNA), lncRNA-PAGBC competitively binds to the tumour suppressive microRNAs miR-133b and miR-511. This competitive role of lncRNA-PAGBC is required for its ability to promote tumour growth and metastasis and to activate the AKT/mTOR pathway. Moreover, lncRNA-PAGBC interacts with polyadenylate binding protein cytoplasmic 1 (PABPC1) and is stabilized by this interaction. This work provides novel insight on the molecular pathogenesis of GBC. Synopsis Long noncoding RNAs play roles in the development and progression of many cancers. In this study the lncRNA PAGBC is identified as promoting tumorigenesis in human gallbladder cancer by competitive binding to the tumour suppressive microRNAs miR-133b and miR-511. LncRNA-PAGBC is up-regulated in GBC and increased levels associate with poor prognosis. LncRNA-PAGBC promotes tumour growth and metastasis, and activates AKT/mTOR signaling by competitively binding to mirR-133b and mirR-511. LncRNA-PAGBC interacts with and is stabilized by the polyadenylate binding protein PABPC1. Graphical Abstract Long noncoding RNAs play roles in the development and progression of many cancers. In this study the lncRNA PAGBC is identified as promoting tumorigenesis in human gallbladder cancer by competitive binding to the tumour suppressive microRNAs miR-133b and miR-511.