MicroRNA-153 is tumor suppressive in glioblastoma stem cells
MicroRNA-153 is tumor suppressive in glioblastoma stem cells
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MicroRNA-153 在胶质母细胞瘤干细胞中具有肿瘤抑制作用
DOI：
10.1007/s11033-012-2278-4
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发表时间：
2013-04-01
影响因子：
2.8
通讯作者：
Wu, Zhaoli
中科院分区：
文献类型：
--
作者：
Zhao, Shiguang;Deng, Yifan;Wu, Zhaoli
多形性胶质母细胞瘤（GBM）是一种致命的脑肿瘤，被认为是由GBM干细胞（GBM-SC）引起的。microRNA进行各种细胞过程的转录后调节，这些细胞过程调节GBM-SC的干性特性。在这里，我们研究了miR-153在GBM-SCs中的关键作用。首先，从六个GBM标本中分离GBM-SC。这些胶质母细胞-干细胞形成胶质母细胞球，表达与神经干细胞相关的标志物，并具有自我更新和多向分化的能力。qRT-PCR分析显示miR-153在GBM组织中的表达相对于正常脑组织下调，在CD 133阳性细胞中的表达相对于CD 133阴性细胞下调。该项目首次证明了将miR-153瞬时转染到GBM-SCs中可以抑制其干细胞特性，例如损害自我更新能力和诱导分化。同时，miR-153还能抑制GBM-SCs的生长，诱导其凋亡。总之，这些结果表明，miR-153表达的再激活提示了GBM-SC的新治疗策略。
Glioblastoma multiforme (GBM) is lethal brain tumor thought to arise from GBM stem cells (GBM-SCs). MicroRNAs carry out post-transcriptional regulation of various cellular processes that modulate the stemness properties of GBM-SCs. Here, we investigated the critical role of miR-153 in GBM-SCs. First, GBM-SCs were isolated from six GBM specimens. These GBM-SCs formed GBM spheres, expressed markers associated with neural stem cells, and possessed the capacity for self-renewal and multilineage differentiation. Then qRT-PCR analysis showed that miR-153 expression was down-regulated in GBM tissues relative to normal brain tissues, and in CD133 positive cells relative to CD133 negative cells. This project demonstrates for the first time that transient transfection of miR-153 into GBM-SCs can inhibit their stemness properties, such as impairing self-renewal ability and inducing differentiation. Meanwhile, miR-153 can also repress GBM-SCs growth and induce apoptosis. Altogether, these results indicate that reactivation of miR-153 expression suggests novel therapeutic strategies for GBM-SCs.