Inhibition of EGR1 inhibits glioma proliferation by targeting CCND1 promoter.
Inhibition of EGR1 inhibits glioma proliferation by targeting CCND1 promoter.
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抑制 EGR1 通过靶向 CCND1 启动子抑制神经胶质瘤增殖
DOI：
10.1186/s13046-017-0656-4
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发表时间：
2017-12-15
期刊：
影响因子：
--
通讯作者：
Li GH
中科院分区：
文献类型：
--
作者：
Chen DG;Zhu B;Lv SQ;Zhu H;Tang J;Huang C;Li Q;Zhou P;Wang DL;Li GH
胶质瘤是中枢神经系统最常见的原发性肿瘤。无论治疗策略的发展如何，胶质瘤患者的预后都很差。其攻击行为主要取决于其强大的增殖能力。转录因子EGR1 （early growth response 1）是锌指转录因子家族的一员，在细胞生长和增殖中起重要作用。采用RT-qPCR和Western-blotting检测39例胶质瘤组织和10例正常脑组织中EGR1的表达水平。通过体外和体内细胞增殖试验评估EGR1对U251细胞、U251干细胞样细胞（GSCs）和U87细胞增殖的影响。通过CHIP实验证实了EGR1与CCND1启动子的特异性结合。EGF用于提高EGR1的表达。与正常脑组织相比，胶质瘤中EGR1表达水平降低，但在所有胶质瘤患者中，EGR1低表达患者的生存率均显著提高。EGR1沉默抑制胶质瘤细胞的增殖并诱导G1期阻滞。EGR1通过直接上调CCND1促进细胞增殖。同时，EGF诱导的EGR1过表达能够促进胶质瘤细胞的增殖。我们的研究结果表明，稳定敲除EGR1可以抑制胶质瘤的增殖。结果表明，与正常组织相比，EGR1在癌组织中表达较低，但可能仍在肿瘤增殖中发挥重要作用。本文的在线版本（10.1186/s13046-017-0656-4）包含补充内容，授权用户可使用。
Gliomas are the most common primary tumors in central nervous system. The prognosis of the patients with glioma is poor regardless of the development of therapeutic strategies. Its aggressive behavior mainly depends on the potent ability of proliferation. The transcription factor EGR1 (early growth response 1) is a member of a zinc finger transcription factor family which plays an essential role in cell growth and proliferation. EGR1 expression levels in 39 glioma tissues and 10 normal brain tissues were tested by RT-qPCR and Western-blotting. The effects of EGR1 on U251 cells, U251 stem-like cells (GSCs), and U87 cells proliferation were assessed using in vitro and in vivo cell proliferation assays. The specific binding between EGR1 and CCND1 promoter was confirmed by CHIP assay. EGF was used to improve EGR1 expression in this assay. EGR1 expression levels in human gliomas are decreased compared with normal brain tissues, however, the patients with low EGR1 expression level showed significantly enhanced patient survival in all glioma patients. EGR1 silencing inhibited proliferation and induced G1 phase arrest in glioma cells. EGR1 contributed to proliferation by directly raising CCND1. Meanwhile, EGR1 overexpression induced by EGF was able to promote the proliferation of glioma cells. Our results show that stable knockdown EGR1 would inhibit glioma proliferation. The results suggest EGR1 showing lower expression in cancer tissues compared with normal tissues maybe still play an important role in tumor proliferation. The online version of this article (10.1186/s13046-017-0656-4) contains supplementary material, which is available to authorized users.
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影响因子：
2.4
作者：
McNeill, Katharine A.
通讯作者：
McNeill, Katharine A.
影响因子：
45.3
作者：
Gilbert, Mark R.;Wang, Meihua;Mehta, Minesh P.
通讯作者：
Mehta, Minesh P.
影响因子：
3.3
作者：
Han, Zheng-Xiang;Wang, Xiao-Xia;Zheng, Jun-Nian
通讯作者：
Zheng, Jun-Nian
DOI：
10.2217/fon.09.67
发表时间：
2009-09
期刊：
Future oncology (London, England)
影响因子：
--
作者：
Gitenay D;Baron VT
通讯作者：
Baron VT
影响因子：
4
作者：
Kaufmann, K;Thiel, G
通讯作者：
Thiel, G