title: LncRNA GClnc1 Promotes Gastric Carcinogenesis and May Act as a Modular Scaffold of WDR5 and KAT2A Complexes to Specify the Histone Modification Pattern.
abstract: Long noncoding RNAs (lncRNA) play a role in carcinogenesis. However, the function of lncRNAs in human gastric cancer remains largely unknown. In this study, we identified a novel lncRNA, GClnc1, which was upregulated and associated with tumorigenesis, tumor size, metastasis, and poor prognosis in gastric cancer. GClnc1 affected gastric cancer cell proliferation, invasiveness, and metastasis in multiple gastric cancer models. Mechanistically, GClnc1 bound WDR5 (a key component of histone methyltransferase complex) and KAT2A histone acetyltransferase, acted as a modular scaffold of WDR5 and KAT2A complexes, coordinated their localization, specified the histone modification pattern on the target genes, including SOD2, and consequently altered gastric cancer cell biology. Thus, GClnc1 is mechanistically, functionally, and clinically oncogenic in gastric cancer. Targeting GClnc1 and its pathway may be meaningful for treating patients with gastric cancer.
  
  
  
  This report documents a novel lncRNA, GClnc1, which may act as a scaffold to recruit the WDR5 and KAT2A complex and modify the transcription of target genes. This study reveals that GClnc1 is an oncogenic lncRNA in human gastric cancer. Cancer Discov; 6(7); 784-801. ©2016 AACR.This article is highlighted in the In This Issue feature, p. 681.
authors.affiliation: State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Division of Gastroenterology and Hepatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, Shanghai, China.
authors.forename: Tian-Tian
authors.initials: TT
authors.lastname: Sun
authors.affiliation: Department of Gastroenterology and Guangzhou Key Laboratory of Digestive Disease, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, China.
authors.forename: Jie
authors.initials: J
authors.lastname: He
authors.affiliation: State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Division of Gastroenterology and Hepatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, Shanghai, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Liang
authors.affiliation: State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Division of Gastroenterology and Hepatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, Shanghai, China.
authors.forename: Lin-Lin
authors.initials: LL
authors.lastname: Ren
authors.affiliation: State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Division of Gastroenterology and Hepatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, Shanghai, China.
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Yan
authors.affiliation: State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Division of Gastroenterology and Hepatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, Shanghai, China.
authors.forename: Ta-Chung
authors.initials: TC
authors.lastname: Yu
authors.affiliation: State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Division of Gastroenterology and Hepatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, Shanghai, China.
authors.forename: Jia-Yin
authors.initials: JY
authors.lastname: Tang
authors.affiliation: State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Division of Gastroenterology and Hepatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, Shanghai, China.
authors.forename: Yu-Jie
authors.initials: YJ
authors.lastname: Bao
authors.affiliation: State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Division of Gastroenterology and Hepatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, Shanghai, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Hu
authors.affiliation: State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Division of Gastroenterology and Hepatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, Shanghai, China. Department of Surgery, University of Michigan School of Medicine, Ann Arbor, Michigan.
authors.forename: Yanwei
authors.initials: Y
authors.lastname: Lin
authors.affiliation: State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Division of Gastroenterology and Hepatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, Shanghai, China. Department of Surgery, University of Michigan School of Medicine, Ann Arbor, Michigan.
authors.forename: Danfeng
authors.initials: D
authors.lastname: Sun
authors.affiliation: State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Division of Gastroenterology and Hepatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, Shanghai, China.
authors.forename: Ying-Xuan
authors.initials: YX
authors.lastname: Chen
authors.affiliation: State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Division of Gastroenterology and Hepatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, Shanghai, China. wzou@med.umich.edu jingyuanfang@sjtu.edu.cn jiehong97@shsmu.edu.cn haoyanchen@shsmu.edu.cn.
authors.forename: Jie
authors.initials: J
authors.lastname: Hong
authors.affiliation: State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Division of Gastroenterology and Hepatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, Shanghai, China. wzou@med.umich.edu jingyuanfang@sjtu.edu.cn jiehong97@shsmu.edu.cn haoyanchen@shsmu.edu.cn.
authors.forename: Haoyan
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Surgery, University of Michigan School of Medicine, Ann Arbor, Michigan. wzou@med.umich.edu jingyuanfang@sjtu.edu.cn jiehong97@shsmu.edu.cn haoyanchen@shsmu.edu.cn.
authors.forename: Weiping
authors.initials: W
authors.lastname: Zou
authors.affiliation: State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Division of Gastroenterology and Hepatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, Shanghai, China. wzou@med.umich.edu jingyuanfang@sjtu.edu.cn jiehong97@shsmu.edu.cn haoyanchen@shsmu.edu.cn.
authors.forename: Jing-Yuan
authors.initials: JY
authors.lastname: Fang
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D047369:Chromatin Immunoprecipitation; D016000:Cluster Analysis; D019295:Computational Biology; D004195:Disease Models, Animal; D018450:Disease Progression; D044127:Epigenesis, Genetic; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D064593:Heterografts; D059014:High-Throughput Nucleotide Sequencing; D051548:Histone Acetyltransferases / Q000378:metabolism*; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D051379:Mice; D008954:Models, Biological; D011485:Protein Binding; D062085:RNA, Long Noncoding / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D013482:Superoxide Dismutase / Q000378:metabolism; D047368:Tumor Burden; D000099156:Superoxide Dismutase 2; D000099224:p300-CBP-Associated Factor
chemical_list: D051548:Histone Acetyltransferases; D011495:Histone-Lysine N-Methyltransferase; D006657:Histones; D047908:Intracellular Signaling Peptides and Proteins; D062085:RNA, Long Noncoding; D013482:Superoxide Dismutase; D000099156:Superoxide Dismutase 2; C502547:WDR5 protein, human; C501179:KAT2A protein, human; D000099224:p300-CBP-Associated Factor