國家衛生研究院 NHRI:Item 3990099045/11643
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    题名: KDM4B is a coactivator of c-Jun and involved in gastric carcinogenesis
    作者: Wu, MC;Cheng, HH;Yeh, TS;Li, YC;Chen, TJ;Sit, WY;Chuu, CP;Kung, HJ;Chien, S;Wang, WC
    贡献者: Institute of Cellular and Systems Medicine;Institute of Molecular and Genomic Medicine
    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 alphaV, 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.
    日期: 2019-01-25
    關聯: Cell Death and Disease. 2019 Jan 25;10(2):Article number 68.
    Link to: http://dx.doi.org/10.1038/s41419-019-1305-y
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=2041-4889&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000457019800011
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85060534854
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