Probes for LONG

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.

The naive embryonic stem cells (nESCs) display unique characteristics compared with the primed counterparts, but the underlying molecular mechanisms remain elusive. Here we investigate the functional roles of Lncenc1, a highly abundant long noncoding RNA in nESCs. Knockdown or knockout of Lncenc1 in mouse nESCs leads to a significantly decreased expression of core pluripotency genes and a significant reduction of colony formation capability. Furthermore, upon the depletion of Lncenc1, the expression of glycolysis-associated genes is significantly reduced, and the glycolytic activity is substantially impaired, as indicated by a more than 50% reduction in levels of glucoseconsumption, lactate production, and extracellular acidification rate. Mechanistically, Lncenc1 interacts with PTBP1 and HNRNPK, which regulate the transcription of glycolytic genes, thereby maintaining the self-renewal of nESCs. Our results demonstrate the functions of Lncenc1 in linking energy metabolism and naive state of ESCs, which may enhance our understanding of the molecular basis underlying naive pluripotency.