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

研究成果: 雜誌貢獻文章同行評審

17 引文 斯高帕斯(Scopus)

摘要

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.
原文英語
文章編號68
期刊Cell Death and Disease
10
發行號2
DOIs
出版狀態已發佈 - 2月 1 2019
對外發佈

ASJC Scopus subject areas

  • 免疫學
  • 細胞與分子神經科學
  • 細胞生物學
  • 癌症研究

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