Loss of MED12 Induces Tumor Dormancy in Human Epithelial Ovarian Cancer via Downregulation of EGFR
Loss of MED12 Induces Tumor Dormancy in Human Epithelial Ovarian Cancer via Downregulation of EGFR
复制标题
MED12 缺失通过 EGFR 下调诱导人上皮性卵巢癌肿瘤休眠
DOI：
10.1158/0008-5472.can-18-0134
复制
发表时间：
2018-07-01
期刊：
影响因子：
11.2
通讯作者：
Fu, Li-Wu
中科院分区：
文献类型：
--
作者：
Luo, Xiao-Lin;Deng, Cheng-Cheng;Fu, Li-Wu
高疾病复发率使上皮卵巢癌（EOC）成为所有妇科恶性肿瘤中死亡的主要原因。这些复发通常是由于肿瘤休眠。在这里，我们将RNA聚合酶II转录介质亚基12（MED12）确定为肿瘤休眠的重要分子调节剂。 Med12敲除（KO）在体外和体内诱导EOC细胞的休眠，微阵列分析表明Med12 KO降低了EGFR的表达。 Med12 KO细胞中EGFR表达的恢复恢复了增殖。另外，与EGFR启动子结合的MED12，相关研究表明，MED12表达与EOC患者样品中的EGFR表达呈正相关。临床数据表明，与反应敏感患者相比，耐化疗患者的MED12水平较低。总体而言，我们的数据表明，MED12在调节EGFR的调节中起着重要作用。 （c）2018 AACR。
A high rate of disease relapse makes epithelial ovarian cancer (EOC) the leading cause of death among all gynecologic malignancies. These relapses are often due to tumor dormancy. Here we identify the RNA polymerase II transcriptional mediator subunit 12 (MED12) as an important molecular regulator of tumor dormancy. MED12 knockout (KO) induced dormancy of EOC cells in vitro and in vivo, and microarray analysis showed that MED12 KO decreased expression of EGFR. Restoration of EGFR expression in MED12 KO cells restored proliferation. Additionally, MED12 bound to the promoter of EGFR, and correlation studies showed that MED12 expression positively correlated with EGFR expression in EOC patient samples. Clinical data demonstrated that chemotherapy-resistant patients expressed lower levels of MED12 compared with responsive patients. Overall, our data show that MED12 plays an important role in regulating dormancy of EOC through regulation of EGFR.Significance: MED12 is identified as a novel, important regulator of tumor dormancy in human ovarian cancer. (C) 2018 AACR.