Retrotransposition of Long Interspersed Nucleotide Element-1 Is Associated with Colitis but Not Tumors in a Murine Colitic Cancer Model
Long interspersed element-1 (L1) is a transposable element that can move within the genome, potentially leading to genome diversity and modified gene function. Although L1 activity in somatic cells is normally suppressed through DNA methylation, some L1s are activated in tumors including colorectal...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Public Library of Science
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4339839/ https://www.ncbi.nlm.nih.gov/pubmed/25710700 http://dx.doi.org/10.1371/journal.pone.0116072 |
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author | Otsubo, Takeshi Okamura, Tadashi Hagiwara, Teruki Ishizaka, Yukihito Dohi, Taeko Kawamura, Yuki I. |
author_facet | Otsubo, Takeshi Okamura, Tadashi Hagiwara, Teruki Ishizaka, Yukihito Dohi, Taeko Kawamura, Yuki I. |
author_sort | Otsubo, Takeshi |
collection | PubMed |
description | Long interspersed element-1 (L1) is a transposable element that can move within the genome, potentially leading to genome diversity and modified gene function. Although L1 activity in somatic cells is normally suppressed through DNA methylation, some L1s are activated in tumors including colorectal carcinoma. However, how L1-retrotransposition (L1-RTP) is involved in gastrointestinal disorders remains to be elucidated. We hypothesized that L1-RTP in somatic cells might contribute to colitis-associated cancer (CAC). To address this, we employed an experimental model of CAC using transgenic L1-reporter mice carrying a human L1-EGFP reporter gene. Mice were subjected to repeated cycles of colitis induced by administration of dextran sodium sulfate (DSS) in drinking water with injection of carcinogen azoxymethane (AOM). L1-RTP levels were measured by a quantitative polymerase chain reaction targeting the newly inserted reporter EGFP in various tissues and cell types, including samples obtained by laser microdissection and cell sorting with flow cytometry. DNA methylation levels of the human L1 promoter were analyzed by bisulfite pyrosequencing. AOM+DSS-treated mice exhibited significantly higher levels of L1-RTP in whole colon tissue during the acute phase of colitis when compared with control naïve mice. L1-RTP levels in whole colon tissue were positively correlated with the histological severity of colitis and degree of neutrophil infiltration into the lamina propria (LP), but not with tumor development in the colon. L1-RTP was enriched in LP mesenchymal cells rather than epithelial cells (ECs), myeloid, or lymphoid cells. DNA methylation levels of the human L1 promoter region showed a negative correlation with L1-RTP levels. L1-RTP was absent from most tumors found in 22-week-old mice. In conclusion, we demonstrated that L1-RTP was induced in the mouse CAC mucosa in accordance with the acute inflammatory response; however, retrotransposition appears not to have direct relevance to colitis-induced cancer initiation. |
format | Online Article Text |
id | pubmed-4339839 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-43398392015-03-04 Retrotransposition of Long Interspersed Nucleotide Element-1 Is Associated with Colitis but Not Tumors in a Murine Colitic Cancer Model Otsubo, Takeshi Okamura, Tadashi Hagiwara, Teruki Ishizaka, Yukihito Dohi, Taeko Kawamura, Yuki I. PLoS One Research Article Long interspersed element-1 (L1) is a transposable element that can move within the genome, potentially leading to genome diversity and modified gene function. Although L1 activity in somatic cells is normally suppressed through DNA methylation, some L1s are activated in tumors including colorectal carcinoma. However, how L1-retrotransposition (L1-RTP) is involved in gastrointestinal disorders remains to be elucidated. We hypothesized that L1-RTP in somatic cells might contribute to colitis-associated cancer (CAC). To address this, we employed an experimental model of CAC using transgenic L1-reporter mice carrying a human L1-EGFP reporter gene. Mice were subjected to repeated cycles of colitis induced by administration of dextran sodium sulfate (DSS) in drinking water with injection of carcinogen azoxymethane (AOM). L1-RTP levels were measured by a quantitative polymerase chain reaction targeting the newly inserted reporter EGFP in various tissues and cell types, including samples obtained by laser microdissection and cell sorting with flow cytometry. DNA methylation levels of the human L1 promoter were analyzed by bisulfite pyrosequencing. AOM+DSS-treated mice exhibited significantly higher levels of L1-RTP in whole colon tissue during the acute phase of colitis when compared with control naïve mice. L1-RTP levels in whole colon tissue were positively correlated with the histological severity of colitis and degree of neutrophil infiltration into the lamina propria (LP), but not with tumor development in the colon. L1-RTP was enriched in LP mesenchymal cells rather than epithelial cells (ECs), myeloid, or lymphoid cells. DNA methylation levels of the human L1 promoter region showed a negative correlation with L1-RTP levels. L1-RTP was absent from most tumors found in 22-week-old mice. In conclusion, we demonstrated that L1-RTP was induced in the mouse CAC mucosa in accordance with the acute inflammatory response; however, retrotransposition appears not to have direct relevance to colitis-induced cancer initiation. Public Library of Science 2015-02-24 /pmc/articles/PMC4339839/ /pubmed/25710700 http://dx.doi.org/10.1371/journal.pone.0116072 Text en © 2015 Otsubo et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Otsubo, Takeshi Okamura, Tadashi Hagiwara, Teruki Ishizaka, Yukihito Dohi, Taeko Kawamura, Yuki I. Retrotransposition of Long Interspersed Nucleotide Element-1 Is Associated with Colitis but Not Tumors in a Murine Colitic Cancer Model |
title | Retrotransposition of Long Interspersed Nucleotide Element-1 Is Associated with Colitis but Not Tumors in a Murine Colitic Cancer Model |
title_full | Retrotransposition of Long Interspersed Nucleotide Element-1 Is Associated with Colitis but Not Tumors in a Murine Colitic Cancer Model |
title_fullStr | Retrotransposition of Long Interspersed Nucleotide Element-1 Is Associated with Colitis but Not Tumors in a Murine Colitic Cancer Model |
title_full_unstemmed | Retrotransposition of Long Interspersed Nucleotide Element-1 Is Associated with Colitis but Not Tumors in a Murine Colitic Cancer Model |
title_short | Retrotransposition of Long Interspersed Nucleotide Element-1 Is Associated with Colitis but Not Tumors in a Murine Colitic Cancer Model |
title_sort | retrotransposition of long interspersed nucleotide element-1 is associated with colitis but not tumors in a murine colitic cancer model |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4339839/ https://www.ncbi.nlm.nih.gov/pubmed/25710700 http://dx.doi.org/10.1371/journal.pone.0116072 |
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