Xiao Zhan Gang, Shen Jing, Zhang Lin, Li Long Fei, Li Ming Xing, Hu Wei, Li Zhi Jie, Cho Chi Hin
Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, 646000, Sichuan, P.R. China.
Rm 521A, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China.
Curr Med Chem. 2016;23(32):3687-3696. doi: 10.2174/0929867323666160725093522.
Aberrant epigenetic reprogramming occurs frequently in the development of tumors. Histone H3 lysine 27 trimethylation (H3K27me3) exerts a repressive epigenetic mark on a large number of genes. UTX and JMJD3 are the only two histone demethylases which activate gene expression via demethylating H3K27me3 to H3K27me2 or H3K27me1. Current studies show that dysregulation of these two proteins are heavily linked to oncogenesis in various tissue types. Accumulating evidence suggested that there is remarkable therapeutic potential of targeting JMJD3 or UTX in different types of cancer. Herein, we shall give a brief review on the functional roles of JMJD3 and UTX in cancers and evaluate the available compounds and agents targeting UTX and JMJD3. Finally, we also discuss the several modalities that target UTX and JMJD3 for cancer therapy. This review will help to develop novel strategies to abolish or restore effects of UTX and JMJD3 in the pathogenesis of cancer.
异常的表观遗传重编程在肿瘤发生过程中频繁出现。组蛋白H3赖氨酸27三甲基化（H3K27me3）对大量基因施加抑制性表观遗传标记。UTX和JMJD3是仅有的两种通过将H3K27me3去甲基化为H3K27me2或H3K27me1来激活基因表达的组蛋白去甲基化酶。目前的研究表明，这两种蛋白的失调与多种组织类型的肿瘤发生密切相关。越来越多的证据表明，靶向JMJD3或UTX在不同类型癌症中具有显著的治疗潜力。在此，我们将简要综述JMJD3和UTX在癌症中的功能作用，并评估靶向UTX和JMJD3的现有化合物和药物。最后，我们还将讨论几种针对UTX和JMJD3的癌症治疗方式。这篇综述将有助于开发新的策略来消除或恢复UTX和JMJD3在癌症发病机制中的作用。
