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

Meng Chen Wu, Hsin Hung Cheng, Ta Sen Yeh, Yi Chen Li, Tsan Jan Chen, Wei Yang Sit, Chih Pin Chuu, Hsing Jien Kung, Shu Chien, Wen Ching Wang

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Article number68
JournalCell Death and Disease
Volume10
Issue number2
DOIs
Publication statusPublished - Feb 1 2019
Externally publishedYes

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Interleukin-8
Stomach
Carcinogenesis
Epigenomics
Helicobacter pylori
Stomach Neoplasms
Histone Demethylases
Genomic Instability
Integrins
Transcriptional Activation
Cell Movement
Therapeutics

ASJC Scopus subject areas

  • Immunology
  • Cellular and Molecular Neuroscience
  • Cell Biology
  • Cancer Research

Cite this

Wu, M. C., Cheng, H. H., Yeh, T. S., Li, Y. C., Chen, T. J., Sit, W. Y., ... Wang, W. C. (2019). KDM4B is a coactivator of c-Jun and involved in gastric carcinogenesis. Cell Death and Disease, 10(2), [68]. https://doi.org/10.1038/s41419-019-1305-y

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.

In: Cell Death and Disease, Vol. 10, No. 2, 68, 01.02.2019.

Research output: Contribution to journalArticle

Wu, MC, Cheng, HH, Yeh, TS, Li, YC, Chen, TJ, Sit, WY, Chuu, CP, Kung, HJ, Chien, S & Wang, WC 2019, 'KDM4B is a coactivator of c-Jun and involved in gastric carcinogenesis', Cell Death and Disease, vol. 10, no. 2, 68. https://doi.org/10.1038/s41419-019-1305-y
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. In: Cell Death and Disease. 2019 ; Vol. 10, No. 2.
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