title: Long noncoding RNA GAPLINC regulates CD44-dependent cell invasiveness and associates with poor prognosis of gastric cancer.
abstract: It is increasingly evident that long noncoding RNAs (lncRNA) have causative roles in carcinogenesis. In this study, we report findings implicating a novel lncRNA in gastric cancer, termed GAPLINC (gastric adenocarcinoma predictive long intergenic noncoding RNA), based on the use of global microarray and in situ hybridization (ISH) analyses to identify aberrantly expressed lncRNA in human gastric cancer specimens. GAPLINC is a 924-bp-long lncRNA that is highly expressed in gastric cancer tissues. GAPLINC suppression and with gene expression profiling in gastric cancer cells revealed alterations in cell migration pathways, with CD44 expression the most highly correlated. Manipulating GAPLINC expression altered CD44 mRNA abundance and the effects of GAPLINC on cell migration and proliferation were neutralized by suppressing CD44 expression. Mechanistic investigations revealed that GAPLINC regulates CD44 as a molecular decoy for miR211-3p, a microRNA that targets both CD44 and GAPLINC. Tissue ISH analysis suggested that GAPLINC overexpression defines a subgroup of patients with gastric cancer with very poor survival. Taken together, our results identify a noncoding regulatory pathway for the CD44 oncogene, shedding new light on the basis for gastric cancer cell invasiveness.
authors.affiliation: State Key Laboratory for Oncogenes and Related Genes; Division of Gastroenterology and Hepatology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Hu
authors.affiliation: State Key Laboratory for Oncogenes and Related Genes; Division of Gastroenterology and Hepatology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Jilin
authors.initials: J
authors.lastname: Wang
authors.affiliation: Shanghai Institute of Digestive Disease, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Shanghai, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Qian
authors.affiliation: State Key Laboratory for Oncogenes and Related Genes; Division of Gastroenterology and Hepatology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Kong
authors.affiliation: State Key Laboratory for Oncogenes and Related Genes; Division of Gastroenterology and Hepatology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Jieting
authors.initials: J
authors.lastname: Tang
authors.affiliation: State Key Laboratory for Oncogenes and Related Genes; Division of Gastroenterology and Hepatology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Yingchao
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Shanghai Institute of Digestive Disease, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Shanghai, China.
authors.forename: Haoyan
authors.initials: H
authors.lastname: Chen
authors.affiliation: Shanghai Institute of Digestive Disease, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Shanghai, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Hong
authors.affiliation: Department of Surgery, University of Michigan, Ann Arbor, Michigan.
authors.forename: Weiping
authors.initials: W
authors.lastname: Zou
authors.affiliation: State Key Laboratory for Oncogenes and Related Genes; Division of Gastroenterology and Hepatology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Yingxuan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: State Key Laboratory for Oncogenes and Related Genes; Division of Gastroenterology and Hepatology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. jiexu@yahoo.com jingyuanfang@yahoo.com.
authors.forename: Jie
authors.initials: J
authors.lastname: Xu
authors.affiliation: State Key Laboratory for Oncogenes and Related Genes; Division of Gastroenterology and Hepatology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. jiexu@yahoo.com jingyuanfang@yahoo.com.
authors.forename: Jing-Yuan
authors.initials: JY
authors.lastname: Fang
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics; D009361:Neoplasm Invasiveness; D011379:Prognosis; D062085:RNA, Long Noncoding / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology*
chemical_list: C497483:CD44 protein, human; D018960:Hyaluronan Receptors; D035683:MicroRNAs; D062085:RNA, Long Noncoding; D012333:RNA, Messenger; D012334:RNA, Neoplasm