Li Haijie, Yang Xi, Wang Guihua, Li Xiaolan, Tao Deding, Hu Junbo, Luo Xuelai
Cancer Research Institute, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China.
Oncotarget. 2016 Sep 6;7(36):57866-57877. doi: 10.18632/oncotarget.11077.
Histone methyltransferases and demethylases regulate transcription by altering the epigenetic marks on histones in tumorigenesis. Members of the histone lysine(K)-specific demethylase 4 (KDM4) family are dysregulated in several types of cancer. Here, we report a novel role for KDM4B in mitochondrial apoptosis. In this study, we demonstrate that KDM4B is overexpressed in colorectal cancer (CRC) tissues. Decreased expression of KDM4B significantly promoted apoptosis of CRC cell lines. Moreover, our data indicate that HAX1 is required for KDM4B-mediated mitochondrial apoptosis. The transcription of HAX1 was directly activated by KDM4B. We also show that HAX1 is overexpressed in CRC tissues and is positively correlated with KMD4B expression. Collectively, we demonstrate that KDM4B may play an important role in mitochondrial apoptosis and represent a potential therapeutic cancer target in CRC.
组蛋白甲基转移酶和去甲基酶通过改变肿瘤发生过程中组蛋白上的表观遗传标记来调节转录。组蛋白赖氨酸（K）特异性去甲基酶4（KDM4）家族的成员在几种类型的癌症中表达失调。在此，我们报道了KDM4B在线粒体凋亡中的新作用。在本研究中，我们证明KDM4B在结直肠癌（CRC）组织中过表达。KDM4B表达的降低显著促进了CRC细胞系的凋亡。此外，我们的数据表明HAX1是KDM4B介导的线粒体凋亡所必需的。HAX1的转录由KDM4B直接激活。我们还表明HAX1在CRC组织中过表达，并且与KMD4B表达呈正相关。总体而言，我们证明KDM4B可能在线粒体凋亡中起重要作用，并代表CRC中一个潜在的治疗性癌症靶点。
