Cargando…

KDM4B is a coactivator of c-Jun and involved in gastric carcinogenesis

KDM4/JMJD2 Jumonji C-containing histone lysine demethylases (KDM4A–D) constitute an important class of epigenetic modulators in the transcriptional activation of cellular processes and genome stability. Interleukin-8 (IL-8) is overexpressed in gastric cancer, but the mechanisms and particularly the...

Descripción completa

Detalles Bibliográficos
Autores principales: Wu, Meng-Chen, Cheng, Hsin-Hung, Yeh, Ta-Sen, Li, Yi-Chen, Chen, Tsan-Jan, Sit, Wei Yang, Chuu, Chih-Pin, Kung, Hsing-Jien, Chien, Shu, Wang, Wen-Ching
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6347645/
https://www.ncbi.nlm.nih.gov/pubmed/30683841
http://dx.doi.org/10.1038/s41419-019-1305-y
_version_ 1783389959398359040
author Wu, Meng-Chen
Cheng, Hsin-Hung
Yeh, Ta-Sen
Li, Yi-Chen
Chen, Tsan-Jan
Sit, Wei Yang
Chuu, Chih-Pin
Kung, Hsing-Jien
Chien, Shu
Wang, Wen-Ching
author_facet Wu, Meng-Chen
Cheng, Hsin-Hung
Yeh, Ta-Sen
Li, Yi-Chen
Chen, Tsan-Jan
Sit, Wei Yang
Chuu, Chih-Pin
Kung, Hsing-Jien
Chien, Shu
Wang, Wen-Ching
author_sort Wu, Meng-Chen
collection PubMed
description KDM4/JMJD2 Jumonji C-containing histone lysine demethylases (KDM4A–D) constitute an important class of epigenetic modulators in the transcriptional activation of cellular processes and genome stability. Interleukin-8 (IL-8) is overexpressed in gastric cancer, but the mechanisms and particularly the role of the epigenetic regulation of IL-8, are unclear. Here, we report that KDM4B, but not KDM4A/4C, upregulated IL-8 production in the absence or presence of Helicobacter pylori. Moreover, KDM4B physically interacts with c-Jun on IL-8, MMP1, and ITGAV promoters via its demethylation activity. The depletion of KDM4B leads to the decreased expression of integrin αV, which is exploited by H. pylori carrying the type IV secretion system, reducing IL-8 production and cell migration. Elevated KDM4B expression is significantly associated with the abundance of p-c-Jun in gastric cancer and is linked to a poor clinical outcome. Together, our results suggest that KDM4B is a key regulator of JNK/c-Jun-induced processes and is a valuable therapeutic target.
format Online
Article
Text
id pubmed-6347645
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-63476452019-01-28 KDM4B is a coactivator of c-Jun and involved in gastric carcinogenesis Wu, Meng-Chen Cheng, Hsin-Hung Yeh, Ta-Sen Li, Yi-Chen Chen, Tsan-Jan Sit, Wei Yang Chuu, Chih-Pin Kung, Hsing-Jien Chien, Shu Wang, Wen-Ching Cell Death Dis Article KDM4/JMJD2 Jumonji C-containing histone lysine demethylases (KDM4A–D) constitute an important class of epigenetic modulators in the transcriptional activation of cellular processes and genome stability. Interleukin-8 (IL-8) is overexpressed in gastric cancer, but the mechanisms and particularly the role of the epigenetic regulation of IL-8, are unclear. Here, we report that KDM4B, but not KDM4A/4C, upregulated IL-8 production in the absence or presence of Helicobacter pylori. Moreover, KDM4B physically interacts with c-Jun on IL-8, MMP1, and ITGAV promoters via its demethylation activity. The depletion of KDM4B leads to the decreased expression of integrin αV, which is exploited by H. pylori carrying the type IV secretion system, reducing IL-8 production and cell migration. Elevated KDM4B expression is significantly associated with the abundance of p-c-Jun in gastric cancer and is linked to a poor clinical outcome. Together, our results suggest that KDM4B is a key regulator of JNK/c-Jun-induced processes and is a valuable therapeutic target. Nature Publishing Group UK 2019-01-25 /pmc/articles/PMC6347645/ /pubmed/30683841 http://dx.doi.org/10.1038/s41419-019-1305-y Text en © The Author(s) 2019 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
Wu, Meng-Chen
Cheng, Hsin-Hung
Yeh, Ta-Sen
Li, Yi-Chen
Chen, Tsan-Jan
Sit, Wei Yang
Chuu, Chih-Pin
Kung, Hsing-Jien
Chien, Shu
Wang, Wen-Ching
KDM4B is a coactivator of c-Jun and involved in gastric carcinogenesis
title KDM4B is a coactivator of c-Jun and involved in gastric carcinogenesis
title_full KDM4B is a coactivator of c-Jun and involved in gastric carcinogenesis
title_fullStr KDM4B is a coactivator of c-Jun and involved in gastric carcinogenesis
title_full_unstemmed KDM4B is a coactivator of c-Jun and involved in gastric carcinogenesis
title_short KDM4B is a coactivator of c-Jun and involved in gastric carcinogenesis
title_sort kdm4b is a coactivator of c-jun and involved in gastric carcinogenesis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6347645/
https://www.ncbi.nlm.nih.gov/pubmed/30683841
http://dx.doi.org/10.1038/s41419-019-1305-y
work_keys_str_mv AT wumengchen kdm4bisacoactivatorofcjunandinvolvedingastriccarcinogenesis
AT chenghsinhung kdm4bisacoactivatorofcjunandinvolvedingastriccarcinogenesis
AT yehtasen kdm4bisacoactivatorofcjunandinvolvedingastriccarcinogenesis
AT liyichen kdm4bisacoactivatorofcjunandinvolvedingastriccarcinogenesis
AT chentsanjan kdm4bisacoactivatorofcjunandinvolvedingastriccarcinogenesis
AT sitweiyang kdm4bisacoactivatorofcjunandinvolvedingastriccarcinogenesis
AT chuuchihpin kdm4bisacoactivatorofcjunandinvolvedingastriccarcinogenesis
AT kunghsingjien kdm4bisacoactivatorofcjunandinvolvedingastriccarcinogenesis
AT chienshu kdm4bisacoactivatorofcjunandinvolvedingastriccarcinogenesis
AT wangwenching kdm4bisacoactivatorofcjunandinvolvedingastriccarcinogenesis