MIR-451 and Imatinib mesylate inhibit tumor growth of Glioblastoma stem cells
MIR-451 and Imatinib mesylate inhibit tumor growth of Glioblastoma stem cells
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DOI：
10.1016/j.bbrc.2008.08.107
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发表时间：
2008-11-07
影响因子：
3.1
通讯作者：
Givol, David
中科院分区：
文献类型：
--
作者：
Gal, Hilah;Pandi, Gopal;Givol, David
我们检查了胶质母细胞瘤干细胞（CD133+）和非干细胞（CD133-）细胞群的microRNA谱，发现CD133-细胞中几种mir上调，包括miR-451、miR-486和miR-425，其中一些可能参与脑分化的调节。用上述mir转染GBM细胞可抑制神经球的形成，转染成熟的miR-451分散神经球可抑制GBM细胞的生长。此外，转染miR-451联合甲磺酸伊马替尼治疗对GBM神经球的分散具有协同作用。此外，我们在miR-451的启动子区域发现了SMAD的靶点，并表明SMAD3和4激活了这样的启动子-荧光素酶结构。在GBM细胞中转染SMAD可抑制其生长，提示SMAD可能通过上调miR-451驱动GBM干细胞向CD133-细胞分化，降低其致瘤性。发现更多的mir和调控GBM干细胞的靶基因可能为治疗提供新的潜在药物。(C) 2008爱思唯尔公司版权所有。
We examined the microRNA profiles of Glioblastoma stem (CD133+) and non-stem (CD133-) cell populations and found up-regulation of several miRs in the CD133- cells, including miR-451, miR-486, and miR-425, some of which may be involved in regulation of brain differentiation. Transfection of GBM cells with the above miRs inhibited neurosphere formation and transfection with the mature miR-451 dispersed neurospheres, and inhibited GBM cell growth. Furthermore, transfection of miR-451 combined with Imatinib mesylate treatment had a cooperative effect in dispersal of GBM neurospheres. in addition, we identified a target site for SMAD in the promoter region of miR-451 and showed that SMAD3 and 4 activate such a promoter-luciferase construct. Transfection of SMAD in GBM cells inhibited their growth, suggesting that SMAD may drive GBM stem cells to differentiate to CD133- cells through up-regulation of miR-451 and reduces their tumorigenicity. Identification of additional miRs and target genes that regulate GBM stem cells may provide new potential drugs for therapy. (C) 2008 Elsevier Inc. All rights reserved.