Yang Rui, Wu Yanan, Wang Mei, Sun Zhongfeng, Zou Jiahua, Zhang Yundong, Cui Hongjuan
State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing 400715, P.R. China.
Department of Neurosurgery, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, P.R. China.
Oncotarget. 2015 Apr 10;6(10):7644-56. doi: 10.18632/oncotarget.3223.
Histone deacetylase 9 (HDAC9), a member of class II HDACs, regulates a wide variety of normal and abnormal physiological functions. We found that HDAC9 is over-expressed in prognostically poor glioblastoma patients. Knockdown HDAC9 decreased proliferation in vitro and tumor formation in vivo. HDAC9 accelerated cell cycle in part by potentiating the EGFR signaling pathway. Also, HDAC9 interacted with TAZ, a key downstream effector of Hippo pathway. Knockdown of HDAC9 decreased the expression of TAZ. We found that overexpressed TAZ in HDAC9-knockdown cells abrogated the effects induced by HDAC9 silencing both in vitro and in vivo. We demonstrated that HDAC9 promotes tumor formation of glioblastoma via TAZ-mediated EGFR pathway activation, and provide the evidence for promising target for the treatment of glioblastoma.
组蛋白去乙酰化酶9（HDAC9）是II类组蛋白去乙酰化酶的成员之一，可调节多种正常和异常的生理功能。我们发现HDAC9在预后不良的胶质母细胞瘤患者中过度表达。敲低HDAC9可降低体外增殖和体内肿瘤形成。HDAC9部分通过增强表皮生长因子受体（EGFR）信号通路来加速细胞周期。此外，HDAC9与Hippo通路的关键下游效应因子TAZ相互作用。敲低HDAC9可降低TAZ的表达。我们发现，在HDAC9敲低的细胞中过表达TAZ可消除HDAC9沉默在体外和体内诱导的效应。我们证明，HDAC9通过TAZ介导的EGFR通路激活促进胶质母细胞瘤的肿瘤形成，并为胶质母细胞瘤治疗的有前景靶点提供了证据。
