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lncRNACNN3-206 activates intestinal epithelial cell apoptosis and invasion by sponging miR-212, an implication for Crohn's disease

BACKGROUND: Statistics indicate that the incidence of Crohn’s disease (CD) is rising in many countries. The poor understanding on the pathological mechanism has limited the development of effective therapy against this disease. Previous studies showed that long noncoding RNAs (lncRNAs) could be invo...

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Autores principales: Li, Na, Shi, Rui-Hua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Baishideng Publishing Group Inc 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7015720/
https://www.ncbi.nlm.nih.gov/pubmed/32089625
http://dx.doi.org/10.3748/wjg.v26.i5.478
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author Li, Na
Shi, Rui-Hua
author_facet Li, Na
Shi, Rui-Hua
author_sort Li, Na
collection PubMed
description BACKGROUND: Statistics indicate that the incidence of Crohn’s disease (CD) is rising in many countries. The poor understanding on the pathological mechanism has limited the development of effective therapy against this disease. Previous studies showed that long noncoding RNAs (lncRNAs) could be involved in autoimmune diseases including CD, but the detailed molecular mechanisms remain unclear. AIM: To identify the differentially expressed lncRNAs in the intestinal mucosa associated with CD, and to characterize their pathogenic role(s) and related mechanisms. METHODS: The differential expression of lncRNAs was screened by high-throughput RNA sequencing, and the top candidate genes were validated in an expanded cohort by real-time PCR. The regulatory network was predicted by bioinformatic software and competitive endogenous RNA analysis, and was characterized in Caco-2 and HT-29 cell culture using methods of cell transfection, real-time PCR, Western blotting analysis, flow cytometry, and cell migration and invasion assays. Finally, these findings were confirmed in vivo using a CD animal model. RESULTS: The 3' end of lncRNACNN3-206 and the 3’ UTR of Caspase10 contain high-affinity miR212 binding sites. lncRNACNN3-206 expression was found to be significantly increased in intestinal lesions of CD patients. Activation of the lncRNACNN3-206-miR-212-Caspase10 regulatory network led to increased apoptosis, migration and invasion in intestinal epithelial cells. Knockdown of lncRNACNN3-206 expression alleviated intestinal mucosal inflammation and tissue damage in the CD mouse model. CONCLUSION: lncRNACNN3-206 may play a key role in CD pathogenesis. lncRNACNN3-206 could be a therapeutic target for CD treatment.
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spelling pubmed-70157202020-02-21 lncRNACNN3-206 activates intestinal epithelial cell apoptosis and invasion by sponging miR-212, an implication for Crohn's disease Li, Na Shi, Rui-Hua World J Gastroenterol Basic Study BACKGROUND: Statistics indicate that the incidence of Crohn’s disease (CD) is rising in many countries. The poor understanding on the pathological mechanism has limited the development of effective therapy against this disease. Previous studies showed that long noncoding RNAs (lncRNAs) could be involved in autoimmune diseases including CD, but the detailed molecular mechanisms remain unclear. AIM: To identify the differentially expressed lncRNAs in the intestinal mucosa associated with CD, and to characterize their pathogenic role(s) and related mechanisms. METHODS: The differential expression of lncRNAs was screened by high-throughput RNA sequencing, and the top candidate genes were validated in an expanded cohort by real-time PCR. The regulatory network was predicted by bioinformatic software and competitive endogenous RNA analysis, and was characterized in Caco-2 and HT-29 cell culture using methods of cell transfection, real-time PCR, Western blotting analysis, flow cytometry, and cell migration and invasion assays. Finally, these findings were confirmed in vivo using a CD animal model. RESULTS: The 3' end of lncRNACNN3-206 and the 3’ UTR of Caspase10 contain high-affinity miR212 binding sites. lncRNACNN3-206 expression was found to be significantly increased in intestinal lesions of CD patients. Activation of the lncRNACNN3-206-miR-212-Caspase10 regulatory network led to increased apoptosis, migration and invasion in intestinal epithelial cells. Knockdown of lncRNACNN3-206 expression alleviated intestinal mucosal inflammation and tissue damage in the CD mouse model. CONCLUSION: lncRNACNN3-206 may play a key role in CD pathogenesis. lncRNACNN3-206 could be a therapeutic target for CD treatment. Baishideng Publishing Group Inc 2020-02-07 2020-02-07 /pmc/articles/PMC7015720/ /pubmed/32089625 http://dx.doi.org/10.3748/wjg.v26.i5.478 Text en ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved. http://creativecommons.org/licenses/by-nc/4.0/ This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial.
spellingShingle Basic Study
Li, Na
Shi, Rui-Hua
lncRNACNN3-206 activates intestinal epithelial cell apoptosis and invasion by sponging miR-212, an implication for Crohn's disease
title lncRNACNN3-206 activates intestinal epithelial cell apoptosis and invasion by sponging miR-212, an implication for Crohn's disease
title_full lncRNACNN3-206 activates intestinal epithelial cell apoptosis and invasion by sponging miR-212, an implication for Crohn's disease
title_fullStr lncRNACNN3-206 activates intestinal epithelial cell apoptosis and invasion by sponging miR-212, an implication for Crohn's disease
title_full_unstemmed lncRNACNN3-206 activates intestinal epithelial cell apoptosis and invasion by sponging miR-212, an implication for Crohn's disease
title_short lncRNACNN3-206 activates intestinal epithelial cell apoptosis and invasion by sponging miR-212, an implication for Crohn's disease
title_sort lncrnacnn3-206 activates intestinal epithelial cell apoptosis and invasion by sponging mir-212, an implication for crohn's disease
topic Basic Study
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7015720/
https://www.ncbi.nlm.nih.gov/pubmed/32089625
http://dx.doi.org/10.3748/wjg.v26.i5.478
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