DNA methylation status of epithelial-mesenchymal transition (EMT)--related genes is associated with severe clinical phenotypes in ulcerative colitis (UC).
BACKGROUND: Epithelial-to-mesenchymal transition (EMT) is a phenomenon that allows the conversion of adherent epithelial cells to a mesenchymal cell phenotype, which enhances migratory capacity and invasiveness. Recent studies have suggested that EMT contributes to the pathogenesis of ulcerative col...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4193736?pdf=render |
| _version_ | 1819044359660634112 |
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| author | Tomomitsu Tahara Tomoyuki Shibata Masaaki Okubo Takamitsu Ishizuka Masakatsu Nakamura Mitsuo Nagasaka Yoshihito Nakagawa Naoki Ohmiya Tomiyasu Arisawa Ichiro Hirata |
| author_facet | Tomomitsu Tahara Tomoyuki Shibata Masaaki Okubo Takamitsu Ishizuka Masakatsu Nakamura Mitsuo Nagasaka Yoshihito Nakagawa Naoki Ohmiya Tomiyasu Arisawa Ichiro Hirata |
| author_sort | Tomomitsu Tahara |
| collection | DOAJ |
| description | BACKGROUND: Epithelial-to-mesenchymal transition (EMT) is a phenomenon that allows the conversion of adherent epithelial cells to a mesenchymal cell phenotype, which enhances migratory capacity and invasiveness. Recent studies have suggested that EMT contributes to the pathogenesis of ulcerative colitis (UC). We investigated the promoter DNA methylation status of EMT-related genes in the colonic mucosa in UC. METHODS: Colonic biopsies were obtained from the rectal inflammatory mucosa of 86 UC patients and the non-inflammatory proximal colonic mucosa of 10 paired patients. Bisulfite pyrosequencing was used to quantify the methylation of 5 candidate CpG island promoters (NEUROG1, CDX1, miR-1247, CDH1, and CDH13) and LINE1. RESULTS: Using an unsupervised hierarchical clustering analysis, inflamed rectal mucosa was well separated from mucosa that appeared normal. The CDH1 and CDH13 promoters were significantly associated with patient age (p = 0.04, 0.03, respectively). A similar trend was found between those genes and the duration of disease (CDH1: p = 0.07, CDH13: p = 0.0002, mean of both: p<0.00001). Several positive associations were found between hypermethylation and severe clinical phenotypes (CDX1 and miR-1247 and a refractory phenotype: p = 0.04 and 0.006, respectively. miR-1247 and CDH1 hyper methylation and a more severe Mayo endoscopic subscore: miR-1247: p = 0.0008, CDH1: p = 0.03, mean of both: p = 0.003). When the severe clinical phenotype was defined as having any of five phenotypes (hospitalized more than twice, highest Mayo endoscopic subscore, steroid dependence, refractory, or a history of surgery) miR-1247 hypermethylation was associated with the same phenotype (p = 0.008). CONCLUSIONS: Our data suggest that variability in the methylation status of EMT-related genes is associated with more severe clinical phenotypes in UC. |
| first_indexed | 2024-12-21T10:11:26Z |
| format | Article |
| id | doaj.art-519b7477ae2949d9b8bd8524f046e340 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-21T10:11:26Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-519b7477ae2949d9b8bd8524f046e3402022-12-21T19:07:42ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-01910e10794710.1371/journal.pone.0107947DNA methylation status of epithelial-mesenchymal transition (EMT)--related genes is associated with severe clinical phenotypes in ulcerative colitis (UC).Tomomitsu TaharaTomoyuki ShibataMasaaki OkuboTakamitsu IshizukaMasakatsu NakamuraMitsuo NagasakaYoshihito NakagawaNaoki OhmiyaTomiyasu ArisawaIchiro HirataBACKGROUND: Epithelial-to-mesenchymal transition (EMT) is a phenomenon that allows the conversion of adherent epithelial cells to a mesenchymal cell phenotype, which enhances migratory capacity and invasiveness. Recent studies have suggested that EMT contributes to the pathogenesis of ulcerative colitis (UC). We investigated the promoter DNA methylation status of EMT-related genes in the colonic mucosa in UC. METHODS: Colonic biopsies were obtained from the rectal inflammatory mucosa of 86 UC patients and the non-inflammatory proximal colonic mucosa of 10 paired patients. Bisulfite pyrosequencing was used to quantify the methylation of 5 candidate CpG island promoters (NEUROG1, CDX1, miR-1247, CDH1, and CDH13) and LINE1. RESULTS: Using an unsupervised hierarchical clustering analysis, inflamed rectal mucosa was well separated from mucosa that appeared normal. The CDH1 and CDH13 promoters were significantly associated with patient age (p = 0.04, 0.03, respectively). A similar trend was found between those genes and the duration of disease (CDH1: p = 0.07, CDH13: p = 0.0002, mean of both: p<0.00001). Several positive associations were found between hypermethylation and severe clinical phenotypes (CDX1 and miR-1247 and a refractory phenotype: p = 0.04 and 0.006, respectively. miR-1247 and CDH1 hyper methylation and a more severe Mayo endoscopic subscore: miR-1247: p = 0.0008, CDH1: p = 0.03, mean of both: p = 0.003). When the severe clinical phenotype was defined as having any of five phenotypes (hospitalized more than twice, highest Mayo endoscopic subscore, steroid dependence, refractory, or a history of surgery) miR-1247 hypermethylation was associated with the same phenotype (p = 0.008). CONCLUSIONS: Our data suggest that variability in the methylation status of EMT-related genes is associated with more severe clinical phenotypes in UC.http://europepmc.org/articles/PMC4193736?pdf=render |
| spellingShingle | Tomomitsu Tahara Tomoyuki Shibata Masaaki Okubo Takamitsu Ishizuka Masakatsu Nakamura Mitsuo Nagasaka Yoshihito Nakagawa Naoki Ohmiya Tomiyasu Arisawa Ichiro Hirata DNA methylation status of epithelial-mesenchymal transition (EMT)--related genes is associated with severe clinical phenotypes in ulcerative colitis (UC). PLoS ONE |
| title | DNA methylation status of epithelial-mesenchymal transition (EMT)--related genes is associated with severe clinical phenotypes in ulcerative colitis (UC). |
| title_full | DNA methylation status of epithelial-mesenchymal transition (EMT)--related genes is associated with severe clinical phenotypes in ulcerative colitis (UC). |
| title_fullStr | DNA methylation status of epithelial-mesenchymal transition (EMT)--related genes is associated with severe clinical phenotypes in ulcerative colitis (UC). |
| title_full_unstemmed | DNA methylation status of epithelial-mesenchymal transition (EMT)--related genes is associated with severe clinical phenotypes in ulcerative colitis (UC). |
| title_short | DNA methylation status of epithelial-mesenchymal transition (EMT)--related genes is associated with severe clinical phenotypes in ulcerative colitis (UC). |
| title_sort | dna methylation status of epithelial mesenchymal transition emt related genes is associated with severe clinical phenotypes in ulcerative colitis uc |
| url | http://europepmc.org/articles/PMC4193736?pdf=render |
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