Knockdown of EHF inhibited the proliferation, invasion and tumorigenesis of ovarian cancer cells
Knockdown of EHF inhibited the proliferation, invasion and tumorigenesis of ovarian cancer cells
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DOI：
10.1002/mc.22349
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发表时间：
2016-06-01
影响因子：
4.6
通讯作者：
Qu, Xiaoyan
中科院分区：
文献类型：
--
作者：
Cheng, Zhongping;Guo, Jing;Qu, Xiaoyan
卵巢癌是世界上最致命的妇科恶性肿瘤。ETS同源因子（EHF）是E26转化特异性（ETS）转录因子中的一员，在卵巢癌中有过表达的报道。然而，EHF在卵巢癌中生物学功能的分子机制仍不清楚。在此，我们发现EHF在卵巢癌组织中的表达高于非肿瘤组织。此外，EHF高表达水平与卵巢癌患者生存时间短相关。在卵巢癌细胞SKOV3和OVCAR3中敲除EHF，显著抑制细胞增殖并增加G1期细胞群。EHF基因敲除后，细胞周期调控蛋白Cyclin B1、Cyclin D1和PCNA表达下调，细胞周期负调控蛋白P21表达上调。此外，抑制EHF在卵巢癌细胞显着诱导细胞凋亡，但损害细胞粘附和细胞侵袭。此外，ERK和AKT的磷酸化水平在EHF敲低细胞中显著降低。最后，体内实验数据显示，EHF基因敲减抑制了裸鼠肿瘤的生长。我们的数据表明，EHF可能是卵巢癌的一个潜在的预后标志物，并通过靶向ERK和AKT信号通路发挥癌基因的作用，这可能成为卵巢癌治疗的新靶点。(c)2015 Wiley Periodicals，Inc.
Ovarian cancer is the most lethal gynecologic malignancy worldwide. ETS homologous factor (EHF), a member of E26 transformation specific (ETS) transcription factors, has been reported overexpressed in ovarian cancer. However, the molecular mechanism underlying the biological function of EHF in ovarian cancer is still unclear. Here, we found that EHF was elevated in ovarian cancer tissues compared with non-tumorous tissues. Moreover, high EHF expression level was correlated with short survival time of patients with ovarian cancer. Knockdown of EHF in ovarian cancer cells, SKOV3 and OVCAR3, significantly inhibited cell proliferation and increased cells population in G1 phase. The proteins promoting cell cycles (Cyclin B1, Cyclin D1, and PCNA) were down-regulated and the protein negatively regulating cell cycle progression (P21) was up-regulated after EHF knockdown. Moreover, inhibition of EHF in ovarian cancer cells dramatically induced cell apoptosis, but impaired cell adhesion and cell invasion. Furthermore, phosphorylation levels of ERK and AKT were notably reduced in EHF knockdown cells. Finally, in vivo data showed that knockdown of EHF inhibited tumor growth in nude mice. Our data indicates that EHF could be a potential prognosis marker for ovarian cancer and work as an oncogene by targeting ERK and AKT signaling, which can serve as a new target for ovarian cancer treatment. (c) 2015 Wiley Periodicals, Inc.