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RNA 干扰下调 Ezh2 表达可诱导 U87 人神经胶质瘤细胞周期停滞于 G0/G1 期并诱导细胞凋亡。

Downregulation of Ezh2 expression by RNA interference induces cell cycle arrest in the G0/G1 phase and apoptosis in U87 human glioma cells.

机构信息

Department of Neurosurgery, Inner Mongolia People's Hospital, Hohhot, PR China.

出版信息

Oncol Rep. 2012 Dec;28(6):2278-84. doi: 10.3892/or.2012.2033. Epub 2012 Sep 17.

DOI:10.3892/or.2012.2033
PMID:22992977
Abstract

The Ezh2 gene is an important member of the polycomb-group (PcG) family. As a newly identified oncogene, the expression of Ezh2 has been shown to be significantly increased in prostate cancer, breast cancer, renal cell carcinoma and hepatic cancer; however, a role for Ezh2 in the occurrence of glioma has not yet been reported. In this study, we found that the Ezh2 gene is highly expressed in U87 human glioma cells. Using RNA interference, we demonstrated that the downregulation of Ezh2 expression in U87 human glioma cells resulted in apoptosis and a cell cycle arrest in the G0/G1 phase. In addition, we found that silencing of the Ezh2 gene altered the mitochondrial membrane potential and promoted the release of cytochrome c from the mitochondria. Furthermore, the reduced expression of Ezh2 altered the Bax and Bcl-2 protein levels and led to the activation of caspase 9 and 3. These results indicate that the apoptosis induced in U87 human glioma cells by the silencing of the Ezh2 gene is related to the mitochondrial pathway.

摘要

Ezh2 基因是多梳抑制复合物(PcG)家族的重要成员。作为一个新发现的癌基因,Ezh2 的表达已被证实显著增加在前列腺癌、乳腺癌、肾细胞癌和肝癌中;然而,Ezh2 在神经胶质瘤发生中的作用尚未报道。在本研究中,我们发现 Ezh2 基因在 U87 人神经胶质瘤细胞中高度表达。通过 RNA 干扰,我们证明了下调 U87 人神经胶质瘤细胞中 Ezh2 的表达导致细胞凋亡和细胞周期停滞在 G0/G1 期。此外,我们发现沉默 Ezh2 基因改变了线粒体膜电位,并促进了细胞色素 c 从线粒体中的释放。此外,Ezh2 的表达减少改变了 Bax 和 Bcl-2 蛋白水平,并导致 caspase 9 和 3 的激活。这些结果表明,Ezh2 基因沉默诱导 U87 人神经胶质瘤细胞凋亡与线粒体途径有关。

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