TY - JOUR
T1 - KDM4B is a coactivator of c-Jun and involved in gastric carcinogenesis
AU - Wu, Meng Chen
AU - Cheng, Hsin Hung
AU - Yeh, Ta Sen
AU - Li, Yi Chen
AU - Chen, Tsan Jan
AU - Sit, Wei Yang
AU - Chuu, Chih Pin
AU - Kung, Hsing Jien
AU - Chien, Shu
AU - Wang, Wen Ching
PY - 2019/2/1
Y1 - 2019/2/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41419-019-1305-y
DO - 10.1038/s41419-019-1305-y
M3 - Article
C2 - 30683841
AN - SCOPUS:85060534854
VL - 10
JO - Cell Death and Disease
JF - Cell Death and Disease
SN - 2041-4889
IS - 2
M1 - 68
ER -
