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UHRF2信使核糖核酸表达在恶性胶质瘤中较低,但沉默该基因会在体外抑制U251胶质瘤细胞的生长。

UHRF2 mRNA expression is low in malignant glioma but silencing inhibits the growth of U251 glioma cells in vitro.

作者信息

Wu Ting-Feng, Zhang Wei, Su Zuo-Peng, Chen San-Song, Chen Gui-Lin, Wei Yong-Xin, Sun Ting, Xie Xue-Shun, Li Bin, Zhou You-Xin, Du Zi-Wei

机构信息

Neurosurgery and Brain and Nerve Research Laboratory, First Affiliated Hospital of Soochow University, Suzhou, China.

出版信息

Asian Pac J Cancer Prev. 2012;13(10):5137-42. doi: 10.7314/apjcp.2012.13.10.5137.

Abstract

UHRF2 is a member of the ubiquitin plant homeo domain RING finger family, which has been proven to be frequently up-regulated in colorectal cancer cells and play a role as an oncogene in breast cancer cells. However, the role of UHRF2 in glioma cells remains unclear. In this study, we performed real-time quantitative PCR on 32 pathologically confirmed glioma samples (grade I, 4 cases; grade II, 11 cases; grade III, 10 cases; and grade IV, 7 cases; according to the 2007 WHO classification system) and four glioma cell lines (A172, U251, U373, and U87). The expression of UHRF2 mRNA was significantly lower in the grade III and grade IV groups compared with the noncancerous brain tissue group, whereas its expression was high in A172, U251, and U373 glioma cell lines. An in vitro assay was performed to investigate the functions of UHRF2. Using a lentivirus-based RNA interference (RNAi) approach, we down-regulated UHRF2 expression in the U251 glioma cell line. This down- regulation led to the inhibition of cell proliferation, an increase in cell apoptosis, and a change of cell cycle distribution, in which S stage cells decreased and G2/M stage cells increased. Our results suggest that UHRF2 may be closely related to tumorigenesis and the development of gliomas.

摘要

UHRF2是泛素植物同源结构域RING指蛋白家族的成员,已被证明在结肠癌细胞中经常上调,并在乳腺癌细胞中作为癌基因发挥作用。然而,UHRF2在胶质瘤细胞中的作用仍不清楚。在本研究中,我们对32例经病理证实的胶质瘤样本(根据2007年世界卫生组织分类系统:I级4例;II级11例;III级10例;IV级7例)和四种胶质瘤细胞系(A172、U251、U373和U87)进行了实时定量PCR。与非癌脑组织组相比,UHRF2 mRNA在III级和IV级组中的表达显著降低,而在A172、U251和U373胶质瘤细胞系中表达较高。进行了一项体外试验以研究UHRF2的功能。使用基于慢病毒的RNA干扰(RNAi)方法,我们下调了U251胶质瘤细胞系中UHRF2的表达。这种下调导致细胞增殖受到抑制,细胞凋亡增加,细胞周期分布发生变化,其中S期细胞减少,G2/M期细胞增加。我们的结果表明,UHRF2可能与胶质瘤的发生和发展密切相关。

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