Li Ziming, Xu Ling, Tang Naiwang, Xu Yunhua, Ye Xiangyun, Shen Shengping, Niu Xiaomin, Lu Shun, Chen Zhiwei
Shanghai Lung Tumor Clinical Medical Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, People's Republic of China.
Department of Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, People's Republic of China.
FEBS Lett. 2014 Aug 25;588(17):3000-7. doi: 10.1016/j.febslet.2014.05.057. Epub 2014 Jun 10.
EZH2 is a key component of the polycomb PRC2 complex and functions as a histone H3 Lys27 (H3K27) trimethyltransferase. Here we show that EZH2 is down-regulated in human non-small cell lung cancer and low EZH2 expression predicts poor survival. Further we demonstrate that EZH2 inhibits lung cancer cell proliferation and colony formation in vitro and growth in vivo. We found that EZH2 binds to the promoter of Nrf2, where it increases H3K27me3 and represses Nrf2 expression. Finally, Nrf2 seems to be essential for the hyper proliferation of lung cancer cells in the absence of EZH2.
EZH2是多梳PRC2复合物的关键组成部分，作为组蛋白H3赖氨酸27（H3K27）三甲基转移酶发挥作用。在此我们表明，EZH2在人类非小细胞肺癌中表达下调，且EZH2低表达预示着较差的生存率。此外，我们证明EZH2在体外抑制肺癌细胞增殖和集落形成，在体内抑制其生长。我们发现EZH2与Nrf2的启动子结合，在该启动子处它增加H3K27me3并抑制Nrf2表达。最后，在缺乏EZH2的情况下，Nrf2似乎对肺癌细胞的过度增殖至关重要。
