P054 LHFPL3-AS2 long non-coding (lncRNA) is reduced in mucosal biopsies of Crohn Disease, and its reduction in tissue culture disrupts epithelial polarity
| Autor: | K Sosnovski, M BenShoShan, T Braun, I Barshack, L Denson, Y Haberman |
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| Rok vydání: | 2022 |
| Předmět: | |
| Zdroj: | Journal of Crohn's and Colitis. 16:i164-i166 |
| ISSN: | 1876-4479 1873-9946 |
| DOI: | 10.1093/ecco-jcc/jjab232.183 |
| Popis: | Background Disruption of apico-basal polarity attenuate Intestinal epithelia barrier and is part of the Epithelial–mesenchymal transition process linked with Crohn Disease (CD). We have defined widespread dysregulation of long non-coding RNAs (lncRNA), known to have cellular regulatory role, in treatment naïve CD ileum including reduction of LHFPL3-AS2. Aim We aimed to explore the effect of LHFPL3-AS2 reduced expression in the context of CD pathogenesis. Methods dCas9/CRISPRi was used for LHFPL3-AS2 knock-down in Caco-2 cells. Transcriptomics, qPCR, western blots, and confocal microscopy was used to evaluate the effect of LHFPL3-AS2 knock-down. Results LHFPL3-AS2 expression in isolated ileum and ascending colon epithelia from controls was significantly higher than in the sigmoid colon, with LHFPL3-AS2 reduction in the ileum of CD cases vs. controls (p=1.5 and FDR corrected p Conclusion Reduced LHFPL3-AS2 in CD epithelia may contribute to attenuated epithelial polarity. Boosting LHFPL3-AS2 lncRNA expression to enable proper epithelial polarity may reverse the initial step in the CD-associated Epithelial–mesenchymal transition process. |
| Databáze: | OpenAIRE |
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