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LncRNA EPR regulates intestinal mucus production and protects against inflammation and tumorigenesis
The long non-coding RNA EPR is expressed in epithelial tissues, binds to chromatin and controls distinct biological activities in mouse mammary gland cells. Because of its high expression in the intestine, in this study we have generated a colon-specific conditional targeted deletion (EPR cKO) to ev...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10250242/ https://www.ncbi.nlm.nih.gov/pubmed/37070602 http://dx.doi.org/10.1093/nar/gkad257 |
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author | Briata, Paola Mastracci, Luca Zapparoli, Ettore Caputo, Luca Ferracci, Elisa Silvestri, Alessandra Garuti, Anna Hamadou, Meriem Hadjer Inga, Alberto Marcaccini, Elisa Grillo, Federica Bucci, Gabriele Puri, Pier Lorenzo Beznoussenko, Galina Mironov, Alexander Chiacchiera, Fulvio Gherzi, Roberto |
author_facet | Briata, Paola Mastracci, Luca Zapparoli, Ettore Caputo, Luca Ferracci, Elisa Silvestri, Alessandra Garuti, Anna Hamadou, Meriem Hadjer Inga, Alberto Marcaccini, Elisa Grillo, Federica Bucci, Gabriele Puri, Pier Lorenzo Beznoussenko, Galina Mironov, Alexander Chiacchiera, Fulvio Gherzi, Roberto |
author_sort | Briata, Paola |
collection | PubMed |
description | The long non-coding RNA EPR is expressed in epithelial tissues, binds to chromatin and controls distinct biological activities in mouse mammary gland cells. Because of its high expression in the intestine, in this study we have generated a colon-specific conditional targeted deletion (EPR cKO) to evaluate EPR in vivo functions in mice. EPR cKO mice display epithelium hyperproliferation, impaired mucus production and secretion, as well as inflammatory infiltration in the proximal portion of the large intestine. RNA sequencing analysis reveals a rearrangement of the colon crypt transcriptome with strong reduction of goblet cell-specific factors including those involved in the synthesis, assembly, transport and control of mucus proteins. Further, colon mucosa integrity and permeability are impaired in EPR cKO mice, and this results in higher susceptibility to dextran sodium sulfate (DSS)-induced colitis and tumor formation. Human EPR is down-regulated in human cancer cell lines as well as in human cancers, and overexpression of EPR in a colon cancer cell line results in enhanced expression of pro-apoptotic genes. Mechanistically, we show that EPR directly interacts with select genes involved in mucus metabolism whose expression is reduced in EPR cKO mice and that EPR deletion causes tridimensional chromatin organization changes. |
format | Online Article Text |
id | pubmed-10250242 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-102502422023-06-10 LncRNA EPR regulates intestinal mucus production and protects against inflammation and tumorigenesis Briata, Paola Mastracci, Luca Zapparoli, Ettore Caputo, Luca Ferracci, Elisa Silvestri, Alessandra Garuti, Anna Hamadou, Meriem Hadjer Inga, Alberto Marcaccini, Elisa Grillo, Federica Bucci, Gabriele Puri, Pier Lorenzo Beznoussenko, Galina Mironov, Alexander Chiacchiera, Fulvio Gherzi, Roberto Nucleic Acids Res RNA and RNA-protein complexes The long non-coding RNA EPR is expressed in epithelial tissues, binds to chromatin and controls distinct biological activities in mouse mammary gland cells. Because of its high expression in the intestine, in this study we have generated a colon-specific conditional targeted deletion (EPR cKO) to evaluate EPR in vivo functions in mice. EPR cKO mice display epithelium hyperproliferation, impaired mucus production and secretion, as well as inflammatory infiltration in the proximal portion of the large intestine. RNA sequencing analysis reveals a rearrangement of the colon crypt transcriptome with strong reduction of goblet cell-specific factors including those involved in the synthesis, assembly, transport and control of mucus proteins. Further, colon mucosa integrity and permeability are impaired in EPR cKO mice, and this results in higher susceptibility to dextran sodium sulfate (DSS)-induced colitis and tumor formation. Human EPR is down-regulated in human cancer cell lines as well as in human cancers, and overexpression of EPR in a colon cancer cell line results in enhanced expression of pro-apoptotic genes. Mechanistically, we show that EPR directly interacts with select genes involved in mucus metabolism whose expression is reduced in EPR cKO mice and that EPR deletion causes tridimensional chromatin organization changes. Oxford University Press 2023-04-18 /pmc/articles/PMC10250242/ /pubmed/37070602 http://dx.doi.org/10.1093/nar/gkad257 Text en © The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | RNA and RNA-protein complexes Briata, Paola Mastracci, Luca Zapparoli, Ettore Caputo, Luca Ferracci, Elisa Silvestri, Alessandra Garuti, Anna Hamadou, Meriem Hadjer Inga, Alberto Marcaccini, Elisa Grillo, Federica Bucci, Gabriele Puri, Pier Lorenzo Beznoussenko, Galina Mironov, Alexander Chiacchiera, Fulvio Gherzi, Roberto LncRNA EPR regulates intestinal mucus production and protects against inflammation and tumorigenesis |
title | LncRNA EPR regulates intestinal mucus production and protects against inflammation and tumorigenesis |
title_full | LncRNA EPR regulates intestinal mucus production and protects against inflammation and tumorigenesis |
title_fullStr | LncRNA EPR regulates intestinal mucus production and protects against inflammation and tumorigenesis |
title_full_unstemmed | LncRNA EPR regulates intestinal mucus production and protects against inflammation and tumorigenesis |
title_short | LncRNA EPR regulates intestinal mucus production and protects against inflammation and tumorigenesis |
title_sort | lncrna epr regulates intestinal mucus production and protects against inflammation and tumorigenesis |
topic | RNA and RNA-protein complexes |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10250242/ https://www.ncbi.nlm.nih.gov/pubmed/37070602 http://dx.doi.org/10.1093/nar/gkad257 |
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