title: Ulcerative Colitis-Associated Long Noncoding RNA, BC012900, Regulates Intestinal Epithelial Cell Apoptosis.
abstract: BACKGROUND
  Long noncoding RNAs (lncRNAs) were recently found to be key regulators of biological functions and associated with human diseases. Thus far, the roles of lncRNAs in inflammatory bowel disease (IBD) remain unknown. We aimed to determine whether lncRNAs are associated with IBD and regulate epithelial cell physiology.
  
  
  METHODS
  lncRNAs microarray and quantitative RT-PCR were performed on 60 sigmoid colon biopsies from patients with active ulcerative colitis (UC) and relevant controls. Localization of lncRNAs was detected by in situ hybridization and on subcellular RNA. The boundaries of BC012900 were assessed by 5' and 3'-rapid amplification of cDNA ends. Apoptosis and proliferation assays were performed on BC012900-expressing construct or siRNA-transfected cells.
  
  
  RESULTS
  We identified 329 lncRNAs with increased and 126 lncRNAs with decreased expression in active UC tissues compared with normal control tissues, including the most significantly upregulated (BC012900, AK001903, and AK023330) and downregulated (BC029135, CDKN2B-AS1, and BC062296) transcripts. We found that most of the lncRNAs are localized to the nucleus. In particular, BC012900 expression was significantly increased in active UC and stimulated by cytokines and pathogenic molecules. Furthermore, BC012900 overexpression in epithelial cells results in a significant inhibition of cell proliferation and an increased susceptibility to apoptosis, which differ from its adjacent gene DUSP4.
  
  
  CONCLUSIONS
  Multiple lncRNAs are differentially expressed in IBD and play a role in regulating cellular physiology. Our results indicate that lncRNAs may be integral modulators of intestinal inflammation associated with IBD and represent novel targets for future therapeutics and diagnostic marker development.
authors.affiliation: *Section of Gastroenterology and Hepatology, Department of Medicine, University of Chicago, Chicago, Illinois; and †Division of Digestive and Liver Diseases, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas.
authors.forename: Feng
authors.initials: F
authors.lastname: Wu
authors.forename: Yong
authors.initials: Y
authors.lastname: Huang
authors.forename: Fengshi
authors.initials: F
authors.lastname: Dong
authors.forename: John H
authors.initials: JH
authors.lastname: Kwon
mesh_terms: D017209:Apoptosis / Q000235:genetics*; D016022:Case-Control Studies; D049109:Cell Proliferation; D002478:Cells, Cultured; D003093:Colitis, Ulcerative / Q000235:genetics / Q000473:pathology*; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology*; D005500:Follow-Up Studies; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000473:pathology*; D062085:RNA, Long Noncoding / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D062085:RNA, Long Noncoding; D012333:RNA, Messenger