Ulcerative Colitis-Associated Long Noncoding RNA, BC012900, Regulates Intestinal Epithelial Cell Apoptosis.
Inflamm Bowel Dis
; 22(4): 782-95, 2016 Apr.
Article
em En
| MEDLINE
| ID: mdl-26937624
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Colite Ulcerativa
/
Apoptose
/
Células Epiteliais
/
RNA Longo não Codificante
/
Intestinos
Tipo de estudo:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Inflamm Bowel Dis
Assunto da revista:
GASTROENTEROLOGIA
Ano de publicação:
2016
Tipo de documento:
Article