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MicroRNA-21 induces loss of 15-hydroxyprostaglandin dehydrogenase in early gastric tubular adenocarcinoma

15-hydroxyprostaglandin dehydrogenase (15-PGDH), the rate-limiting enzyme in prostaglandin E2 degradation, is decreased in gastric cancers and microRNA (miR)-21 is one of the regulators. We investigated the expression and regulation of 15-PGDH in eary gastric carcinogenesis utilizing endoscopic subm...

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Autores principales: Park, Young Soo, Lee, Jeong Hoon, Jung, Deok-Beom, Kim, Han-Byul, Jung, Jin-Hak, Pak, Sehyung, Ryu, Yeon-Mi, Park, Hye Jin, Park, Yun-Yong, Jung, Hwoon-Yong, Myung, Seung-Jae
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6286338/
https://www.ncbi.nlm.nih.gov/pubmed/30531928
http://dx.doi.org/10.1038/s41598-018-36139-z
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author Park, Young Soo
Lee, Jeong Hoon
Jung, Deok-Beom
Kim, Han-Byul
Jung, Jin-Hak
Pak, Sehyung
Ryu, Yeon-Mi
Park, Hye Jin
Park, Yun-Yong
Jung, Hwoon-Yong
Myung, Seung-Jae
author_facet Park, Young Soo
Lee, Jeong Hoon
Jung, Deok-Beom
Kim, Han-Byul
Jung, Jin-Hak
Pak, Sehyung
Ryu, Yeon-Mi
Park, Hye Jin
Park, Yun-Yong
Jung, Hwoon-Yong
Myung, Seung-Jae
author_sort Park, Young Soo
collection PubMed
description 15-hydroxyprostaglandin dehydrogenase (15-PGDH), the rate-limiting enzyme in prostaglandin E2 degradation, is decreased in gastric cancers and microRNA (miR)-21 is one of the regulators. We investigated the expression and regulation of 15-PGDH in eary gastric carcinogenesis utilizing endoscopic submucosal dissection (ESD) and gastric cancer cell lines. Expression of 15-PGDH and cyclooxygenase-2 as well as the promoter methylation of 15-PGDH were evaluted. CRISPR, miR-21 transfection, proliferation and apoptosis assays were also done. We observed significant decreases in 15-PGDH expression but no promoter methylation was detected in any ESDs. 15-PGDH suppression by CRISPR induced enhanced growth kinetics. miR-21, which was detected in high level in gastric tumors from the TGCA data, caused increased proliferation, decreased apoptosis. miR-21 overexpression was confirmed with CISH and RT-PCR in the ESDs. Loss of 15-PGDH occurs at the very early stage of gastric adenocarcinoma by miR-21. H. pylori infection may affect miR-21 up regulation. Maintaining 15-PGDH enzyme activity could be a new strategic measure in preventing gastric cancer especially tubular adenocarcinoma.
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spelling pubmed-62863382018-12-19 MicroRNA-21 induces loss of 15-hydroxyprostaglandin dehydrogenase in early gastric tubular adenocarcinoma Park, Young Soo Lee, Jeong Hoon Jung, Deok-Beom Kim, Han-Byul Jung, Jin-Hak Pak, Sehyung Ryu, Yeon-Mi Park, Hye Jin Park, Yun-Yong Jung, Hwoon-Yong Myung, Seung-Jae Sci Rep Article 15-hydroxyprostaglandin dehydrogenase (15-PGDH), the rate-limiting enzyme in prostaglandin E2 degradation, is decreased in gastric cancers and microRNA (miR)-21 is one of the regulators. We investigated the expression and regulation of 15-PGDH in eary gastric carcinogenesis utilizing endoscopic submucosal dissection (ESD) and gastric cancer cell lines. Expression of 15-PGDH and cyclooxygenase-2 as well as the promoter methylation of 15-PGDH were evaluted. CRISPR, miR-21 transfection, proliferation and apoptosis assays were also done. We observed significant decreases in 15-PGDH expression but no promoter methylation was detected in any ESDs. 15-PGDH suppression by CRISPR induced enhanced growth kinetics. miR-21, which was detected in high level in gastric tumors from the TGCA data, caused increased proliferation, decreased apoptosis. miR-21 overexpression was confirmed with CISH and RT-PCR in the ESDs. Loss of 15-PGDH occurs at the very early stage of gastric adenocarcinoma by miR-21. H. pylori infection may affect miR-21 up regulation. Maintaining 15-PGDH enzyme activity could be a new strategic measure in preventing gastric cancer especially tubular adenocarcinoma. Nature Publishing Group UK 2018-12-07 /pmc/articles/PMC6286338/ /pubmed/30531928 http://dx.doi.org/10.1038/s41598-018-36139-z Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Park, Young Soo
Lee, Jeong Hoon
Jung, Deok-Beom
Kim, Han-Byul
Jung, Jin-Hak
Pak, Sehyung
Ryu, Yeon-Mi
Park, Hye Jin
Park, Yun-Yong
Jung, Hwoon-Yong
Myung, Seung-Jae
MicroRNA-21 induces loss of 15-hydroxyprostaglandin dehydrogenase in early gastric tubular adenocarcinoma
title MicroRNA-21 induces loss of 15-hydroxyprostaglandin dehydrogenase in early gastric tubular adenocarcinoma
title_full MicroRNA-21 induces loss of 15-hydroxyprostaglandin dehydrogenase in early gastric tubular adenocarcinoma
title_fullStr MicroRNA-21 induces loss of 15-hydroxyprostaglandin dehydrogenase in early gastric tubular adenocarcinoma
title_full_unstemmed MicroRNA-21 induces loss of 15-hydroxyprostaglandin dehydrogenase in early gastric tubular adenocarcinoma
title_short MicroRNA-21 induces loss of 15-hydroxyprostaglandin dehydrogenase in early gastric tubular adenocarcinoma
title_sort microrna-21 induces loss of 15-hydroxyprostaglandin dehydrogenase in early gastric tubular adenocarcinoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6286338/
https://www.ncbi.nlm.nih.gov/pubmed/30531928
http://dx.doi.org/10.1038/s41598-018-36139-z
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