Retinoblastoma protein-interacting zinc-finger gene 1 (RIZ1) dysregulation in human malignant meningiomas
Retinoblastoma protein-interacting zinc-finger gene 1 (RIZ1) dysregulation in human malignant meningiomas
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DOI：
10.1038/onc.2012.155
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发表时间：
2013-03-07
期刊：
影响因子：
8
通讯作者：
Hu, G. H.
中科院分区：
文献类型：
--
作者：
Liu, Z. Y.;Wang, J. Y.;Hu, G. H.
视网膜母细胞瘤蛋白相互作用锌指基因1(RIZ1)在多种类型的人类肿瘤中经常被沉默表达。然而，RIZ1的表达与恶性脑膜瘤的关系尚不清楚。在这里，我们通过对Affymetrix基因芯片微阵列数据的广泛分析，首次发现RIZ1基因的表达与脑膜瘤的进展有关。进一步验证基因表达的方法包括定量聚合酶链式反应(QPCR)、免疫印迹和免疫组织化学分析，这些方法证实RIZ1在恶性脑膜瘤组织中显著下调，与良性脑膜瘤相比。另外，采用慢病毒介导的方法将外源RIZ1基因稳定地导入恶性脑膜瘤细胞，并进行体外5-溴-2-脱氧尿苷掺入实验、集落形成实验、细胞周期分析、侵袭实验、细胞凋亡实验和Western印迹分析。我们的结果表明，RIZ1在恶性脑膜瘤细胞系中的强制表达抑制了细胞的增殖，并将细胞停滞在细胞周期的G2/M期。我们还证实了RIZ1的过表达可能诱导了恶性脑膜瘤细胞的凋亡。此外，RIZ1在恶性脑膜瘤细胞中的过表达与c-myc表达下调有关。我们的研究结果表明，随着脑膜瘤形成的进展，RIZ1的表达显著下调，提示RIZ1可能是一个有希望的候选肿瘤抑制基因，有助于恶性脑膜瘤的发生。Oncogene(2013年)32,1216-1222；doi：10.1038/onc.2012.155；2012年5月21日在线发布
Retinoblastoma protein-interacting zinc-finger gene 1 (RIZ1) expression is often silenced in many types of human tumors. However, the relationship between RIZ1 expression and malignant meningiomas remains unclear. Here we have found for the first time that the expression of RIZ1 genes are associated with meningiomas progression through extensive analyses of Affymetrix GeneChip microarray data. Further validation methods for gene expression included quantitative PCR (qPCR), western blot and immunohistochemistry analysis, and these methods confirmed that RIZ1 is significantly downregulated in malignant meningioma tissues, as compared with benign meningiomas. In addition, malignant meningioma cells were stably transfected with ectogenic RIZ1 using Lentivirus-mediated transfection, and the transfections were followed by an in vitro 5-bromo-2-deoxyuridin incorporation assay, colony formation assay, cell cycle analysis, invasive analysis, apoptotic assay and western blot analysis. Our results demonstrate that the forced expression of RIZ1 in a malignant meningioma cell line inhibited cellular proliferation and arrested the cells in the G2/M phase of the cell cycle. We also confirmed that overexpression of RIZ1 may induce apoptosis of malignant meningioma cells. Furthermore, RIZ1 overexpression in malignant meningioma cells was associated with the downregulation of c-myc expression. These results from our study indicate that RIZ1 expression is significantly downregulated as the formation of meningiomas progressed, and suggest that RIZ1 may represent a promising candidate tumor suppressor gene that contributes to malignant meningiomas. Oncogene (2013) 32, 1216-1222; doi:10.1038/onc.2012.155; published online 21 May 2012