PMID- 31752906 OWN - NLM STAT- MEDLINE DCOM- 20200415 LR - 20220416 IS - 1476-4598 (Electronic) IS - 1476-4598 (Linking) VI - 18 IP - 1 DP - 2019 Nov 21 TI - LncRNA-HGBC stabilized by HuR promotes gallbladder cancer progression by regulating miR-502-3p/SET/AKT axis. PG - 167 LID - 10.1186/s12943-019-1097-9 [doi] LID - 167 AB - BACKGROUNDS: Long non-coding RNAs (lncRNAs) are essential factors that regulate tumor development and metastasis via diverse molecular mechanisms in a broad type of cancers. However, the pathological roles of lncRNAs in gallbladder carcinoma (GBC) remain largely unknown. Here we discovered a novel lncRNA termed lncRNA Highly expressed in GBC (lncRNA-HGBC) which was upregulated in GBC tissue and aimed to investigate its role and regulatory mechanism in the development and progression of GBC. METHODS: The expression level of lncRNA-HGBC in GBC tissue and different cell lines was determined by quantitative real-time PCR. The full length of lncRNA-HGBC was obtained by 5' and 3' rapid amplification of the cDNA ends (RACE). Cellular localization of lncRNA-HGBC was detected by fluorescence in situ hybridization (FISH) assays and subcellular fractionation assay. In vitro and in vivo assays were preformed to explore the biological effects of lncRNA-HGBC in GBC cells. RNA pull-down assay, mass spectrometry, and RNA immunoprecipitation (RIP) assay were used to identify lncRNA-HGBC-interacting proteins. Dual luciferase reporter assays, AGO2-RIP, and MS2-RIP assays were performed to verify the interaction between lncRNA-HGBC and miR-502-3p. RESULTS: We found that lncRNA-HGBC was upregulated in GBC and its upregulation could predict poor survival. Overexpression or knockdown of lncRNA-HGBC in GBC cell lines resulted in increased or decreased, respectively, cell proliferation and invasion in vitro and in xenografted tumors. LncRNA-HGBC specifically bound to RNA binding protein Hu Antigen R (HuR) that in turn stabilized lncRNA-HGBC. LncRNA-HGBC functioned as a competitive endogenous RNA to bind to miR-502-3p that inhibits target gene SET. Overexpression, knockdown or mutation of lncRNA-HGBC altered the inhibitory effects of miR-502-3p on SET expression and downstream activation of AKT. Clinically, lncRNA-HGBC expression was negatively correlated with miR-502-3p, but positively correlated with SET and HuR in GBC tissue. CONCLUSIONS: Our study demonstrates that lncRNA-HGBC promotes GBC metastasis via activation of the miR-502-3p-SET-AKT cascade, pointing to lncRNA-HGBC as a new prognostic predictor and a therapeutic target. FAU - Hu, Yun-Ping AU - Hu YP AD - Department of General Surgery, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Building 25, Room 513, 1665 Kongjiang Road, Shanghai, 200092, China. AD - Shanghai Key Laboratory of Biliary Tract Disease Research, 1665 Kongjiang Road, Shanghai, 200092, China. AD - Shanghai Research Center of Biliary Tract Disease, 1665 Kongjiang Road, Shanghai, 200092, China. AD - Department of Pharmacology, Shanghai Jiao Tong University School of Medicine, W. Building 3, Room 407, 280 Chongqi Road, Shanghai, 200025, China. FAU - Jin, Yun-Peng AU - Jin YP AD - Department of General Surgery, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Building 25, Room 513, 1665 Kongjiang Road, Shanghai, 200092, China. AD - Shanghai Key Laboratory of Biliary Tract Disease Research, 1665 Kongjiang Road, Shanghai, 200092, China. AD - Shanghai Research Center of Biliary Tract Disease, 1665 Kongjiang Road, Shanghai, 200092, China. FAU - Wu, Xiang-Song AU - Wu XS AD - Department of General Surgery, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Building 25, Room 513, 1665 Kongjiang Road, Shanghai, 200092, China. AD - Shanghai Key Laboratory of Biliary Tract Disease Research, 1665 Kongjiang Road, Shanghai, 200092, China. AD - Shanghai Research Center of Biliary Tract Disease, 1665 Kongjiang Road, Shanghai, 200092, China. FAU - Yang, Yang AU - Yang Y AD - Department of General Surgery, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Building 25, Room 513, 1665 Kongjiang Road, Shanghai, 200092, China. AD - Shanghai Key Laboratory of Biliary Tract Disease Research, 1665 Kongjiang Road, Shanghai, 200092, China. AD - Shanghai Research Center of Biliary Tract Disease, 1665 Kongjiang Road, Shanghai, 200092, China. FAU - Li, Yong-Sheng AU - Li YS AD - Department of General Surgery, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Building 25, Room 513, 1665 Kongjiang Road, Shanghai, 200092, China. AD - Shanghai Key Laboratory of Biliary Tract Disease Research, 1665 Kongjiang Road, Shanghai, 200092, China. AD - Shanghai Research Center of Biliary Tract Disease, 1665 Kongjiang Road, Shanghai, 200092, China. FAU - Li, Huai-Feng AU - Li HF AD - Department of General Surgery, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Building 25, Room 513, 1665 Kongjiang Road, Shanghai, 200092, China. AD - Shanghai Key Laboratory of Biliary Tract Disease Research, 1665 Kongjiang Road, Shanghai, 200092, China. AD - Shanghai Research Center of Biliary Tract Disease, 1665 Kongjiang Road, Shanghai, 200092, China. FAU - Xiang, Shan-Shan AU - Xiang SS AD - Department of General Surgery, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Building 25, Room 513, 1665 Kongjiang Road, Shanghai, 200092, China. AD - Shanghai Key Laboratory of Biliary Tract Disease Research, 1665 Kongjiang Road, Shanghai, 200092, China. AD - Shanghai Research Center of Biliary Tract Disease, 1665 Kongjiang Road, Shanghai, 200092, China. FAU - Song, Xiao-Ling AU - Song XL AD - Department of General Surgery, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Building 25, Room 513, 1665 Kongjiang Road, Shanghai, 200092, China. AD - Shanghai Key Laboratory of Biliary Tract Disease Research, 1665 Kongjiang Road, Shanghai, 200092, China. AD - Shanghai Research Center of Biliary Tract Disease, 1665 Kongjiang Road, Shanghai, 200092, China. FAU - Jiang, Lin AU - Jiang L AD - Department of General Surgery, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Building 25, Room 513, 1665 Kongjiang Road, Shanghai, 200092, China. AD - Shanghai Key Laboratory of Biliary Tract Disease Research, 1665 Kongjiang Road, Shanghai, 200092, China. AD - Shanghai Research Center of Biliary Tract Disease, 1665 Kongjiang Road, Shanghai, 200092, China. FAU - Zhang, Yi-Jian AU - Zhang YJ AD - Department of General Surgery, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Building 25, Room 513, 1665 Kongjiang Road, Shanghai, 200092, China. AD - Shanghai Key Laboratory of Biliary Tract Disease Research, 1665 Kongjiang Road, Shanghai, 200092, China. AD - Shanghai Research Center of Biliary Tract Disease, 1665 Kongjiang Road, Shanghai, 200092, China. FAU - Huang, Wen AU - Huang W AD - Department of General Surgery, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Building 25, Room 513, 1665 Kongjiang Road, Shanghai, 200092, China. AD - Shanghai Key Laboratory of Biliary Tract Disease Research, 1665 Kongjiang Road, Shanghai, 200092, China. AD - Shanghai Research Center of Biliary Tract Disease, 1665 Kongjiang Road, Shanghai, 200092, China. FAU - Chen, Shi-Li AU - Chen SL AD - Department of General Surgery, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Building 25, Room 513, 1665 Kongjiang Road, Shanghai, 200092, China. AD - Shanghai Key Laboratory of Biliary Tract Disease Research, 1665 Kongjiang Road, Shanghai, 200092, China. AD - Shanghai Research Center of Biliary Tract Disease, 1665 Kongjiang Road, Shanghai, 200092, China. FAU - Liu, Fa-Tao AU - Liu FT AD - Department of General Surgery, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Building 25, Room 513, 1665 Kongjiang Road, Shanghai, 200092, China. AD - Shanghai Key Laboratory of Biliary Tract Disease Research, 1665 Kongjiang Road, Shanghai, 200092, China. AD - Shanghai Research Center of Biliary Tract Disease, 1665 Kongjiang Road, Shanghai, 200092, China. FAU - Chen, Chen AU - Chen C AD - Department of General Surgery, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Building 25, Room 513, 1665 Kongjiang Road, Shanghai, 200092, China. AD - Shanghai Key Laboratory of Biliary Tract Disease Research, 1665 Kongjiang Road, Shanghai, 200092, China. AD - Shanghai Research Center of Biliary Tract Disease, 1665 Kongjiang Road, Shanghai, 200092, China. FAU - Zhu, Qin AU - Zhu Q AD - Department of General Surgery, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Building 25, Room 513, 1665 Kongjiang Road, Shanghai, 200092, China. AD - Shanghai Key Laboratory of Biliary Tract Disease Research, 1665 Kongjiang Road, Shanghai, 200092, China. AD - Shanghai Research Center of Biliary Tract Disease, 1665 Kongjiang Road, Shanghai, 200092, China. FAU - Chen, Hong-Zhuan AU - Chen HZ AD - Department of Pharmacology, Shanghai Jiao Tong University School of Medicine, W. Building 3, Room 407, 280 Chongqi Road, Shanghai, 200025, China. yaoli@shsmu.edu.cn. FAU - Shao, Rong AU - Shao R AD - Department of General Surgery, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Building 25, Room 513, 1665 Kongjiang Road, Shanghai, 200092, China. rongshao@sjtu.edu.cn. AD - Department of Pharmacology, Shanghai Jiao Tong University School of Medicine, W. Building 3, Room 407, 280 Chongqi Road, Shanghai, 200025, China. rongshao@sjtu.edu.cn. FAU - Liu, Ying-Bin AU - Liu YB AUID- ORCID: 0000-0002-1075-1890 AD - Department of General Surgery, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Building 25, Room 513, 1665 Kongjiang Road, Shanghai, 200092, China. liuyingbin@xinhuamed.com.cn. AD - Shanghai Key Laboratory of Biliary Tract Disease Research, 1665 Kongjiang Road, Shanghai, 200092, China. liuyingbin@xinhuamed.com.cn. AD - Shanghai Research Center of Biliary Tract Disease, 1665 Kongjiang Road, Shanghai, 200092, China. liuyingbin@xinhuamed.com.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20191121 PL - England TA - Mol Cancer JT - Molecular cancer JID - 101147698 RN - 0 (Biomarkers, Tumor) RN - 0 (DNA-Binding Proteins) RN - 0 (ELAV-Like Protein 1) RN - 0 (ELAVL1 protein, human) RN - 0 (Histone Chaperones) RN - 0 (MIRN502 microRNA, human) RN - 0 (MicroRNAs) RN - 0 (RNA, Long Noncoding) RN - 0 (SET protein, human) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) SB - IM EIN - Mol Cancer. 2021 Aug 28;20(1):110. PMID: 34454521 MH - Adult MH - Aged MH - Biomarkers, Tumor MH - Cell Line, Tumor MH - Cell Proliferation MH - DNA-Binding Proteins/*genetics/metabolism MH - Disease Progression MH - ELAV-Like Protein 1/*genetics MH - Female MH - Gallbladder Neoplasms/*genetics/metabolism/pathology MH - *Gene Expression Regulation, Neoplastic MH - Histone Chaperones/*genetics/metabolism MH - Humans MH - Male MH - MicroRNAs/*genetics MH - Middle Aged MH - Neoplasm Metastasis MH - Neoplasm Staging MH - Prognosis MH - Proto-Oncogene Proteins c-akt/*genetics/metabolism MH - RNA Interference MH - RNA, Long Noncoding/*genetics PMC - PMC6868746 OTO - NOTNLM OT - Gallbladder cancer OT - HuR OT - SET OT - lncRNA-HGBC OT - miR-502-3p COIS- The authors declare that they have no competing interests. EDAT- 2019/11/23 06:00 MHDA- 2020/04/16 06:00 PMCR- 2019/11/21 CRDT- 2019/11/23 06:00 PHST- 2019/06/24 00:00 [received] PHST- 2019/11/04 00:00 [accepted] PHST- 2019/11/23 06:00 [entrez] PHST- 2019/11/23 06:00 [pubmed] PHST- 2020/04/16 06:00 [medline] PHST- 2019/11/21 00:00 [pmc-release] AID - 10.1186/s12943-019-1097-9 [pii] AID - 1097 [pii] AID - 10.1186/s12943-019-1097-9 [doi] PST - epublish SO - Mol Cancer. 2019 Nov 21;18(1):167. doi: 10.1186/s12943-019-1097-9.