The tumor suppressor gene rap1GAP is silenced by miR-101-mediated EZH2 overexpression in invasive squamous cell carcinoma.
The tumor suppressor gene rap1GAP is silenced by miR-101-mediated EZH2 overexpression in invasive squamous cell carcinoma.
复制标题
DOI：
10.1038/onc.2011.141
复制
发表时间：
2011-10-20
期刊：
影响因子：
8
通讯作者：
D'Silva, N. J.
中科院分区：
文献类型：
--
作者：
Banerjee, R.;Mani, R-S;Russo, N.;Scanlon, C. S.;Tsodikov, A.;Jing, X.;Cao, Q.;Palanisamy, N.;Metwally, T.;Inglehart, R. C.;Tomlins, S.;Bradford, C.;Carey, T.;Wolf, G.;Kalyana-Sundaram, S.;Chinnaiyan, A. M.;Varambally, S.;D'Silva, N. J.
Rap 1GAP是一种重要的肿瘤抑制基因，在头颈部鳞状细胞癌、黑色素瘤和胰腺癌等多种侵袭性癌症中下调。然而，rap 1GAP在癌症中下调的机制基础知之甚少。通过采用一种综合的方法，我们证明了polycomb介导的rap 1GAP的抑制，涉及EZH 2，头颈部癌症中的组蛋白甲基转移酶。我们进一步证明了miR-101表达的缺失与EZH 2上调相关，并且在头颈癌中伴随rap 1GAP的下调。EZH 2通过促进H3 K27的三甲基化（基因抑制的标志）以及rap 1GAP启动子的超甲基化来抑制rap 1GAP。这些结果提供了一个概念框架，涉及microRNA-癌基因-肿瘤抑制轴，以了解头颈部癌症的进展。
Rap1GAP is a critical tumor suppressor gene that is down-regulated in multiple aggressive cancers such as head and neck squamous cell carcinoma, melanoma and pancreatic cancer. However, the mechanistic basis of rap1GAP down-regulation in cancers is poorly understood. By employing an integrative approach, we demonstrate polycomb mediated repression of rap1GAP that involves EZH2, a histone methyltransferase in head and neck cancers. We further demonstrate that the loss of miR-101 expression correlates with EZH2 up-regulation, and the concomitant down-regulation of rap1GAP in head and neck cancers. EZH2 represses rap1GAP by facilitating the trimethylation of H3K27, a mark of gene repression, and also hypermethylation of rap1GAP promoter. These results provide a conceptual framework involving a microRNA-oncogene-tumor suppressor axis to understand head and neck cancer progression.
登录
查看更多内容
影响因子：
6.4
作者：
He, Li-Ru;Liu, Meng-Zhong;Xie, Dan
通讯作者：
Xie, Dan
DOI：
10.1083/jcb.148.6.1151
发表时间：
2000-03-20
期刊：
The Journal of cell biology
影响因子：
--
作者：
Reedquist KA;Ross E;Koop EA;Wolthuis RM;Zwartkruis FJ;van Kooyk Y;Salmon M;Buckley CD;Bos JL
通讯作者：
Bos JL
影响因子：
64.5
作者：
RUBINFELD, B;MUNEMITSU, S;POLAKIS, P
通讯作者：
POLAKIS, P
DOI：
10.1073/pnas.95.13.7475
发表时间：
1998-06-23
影响因子：
11.1
作者：
Altschuler, DL;Ribeiro-Neto, F
通讯作者：
Ribeiro-Neto, F
体细胞突变改变生发中心起源的滤泡性和弥漫性大 B 细胞淋巴瘤中的 EZH2 (Tyr641)。
影响因子：
30.8
作者：
Morin, Ryan D.;Johnson, Nathalie A.;Severson, Tesa M.;Mungall, Andrew J.;An, Jianghong;Goya, Rodrigo;Paul, Jessica E.;Boyle, Merrill;Woolcock, Bruce W.;Kuchenbauer, Florian;Yap, Damian;Humphries, R. Keith;Griffith, Obi L.;Shah, Sohrab;Zhu, Henry;Kimbara, Michelle;Shashkin, Pavel;Charlot, Jean F.;Tcherpakov, Marianna;Corbett, Richard;Tam, Angela;Varhol, Richard;Smailus, Duane;Moksa, Michelle;Zhao, Yongjun;Delaney, Allen;Qian, Hong;Birol, Inanc;Schein, Jacqueline;Moore, Richard;Holt, Robert;Horsman, Doug E.;Connors, Joseph M.;Jones, Steven;Aparicio, Samuel;Hirst, Martin;Gascoyne, Randy D.;Marra, Marco A.
通讯作者：
Marra, Marco A.