Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, Heilongjiang, People's Republic of China.
Mol Biol Rep. 2013 Apr;40(4):2789-98. doi: 10.1007/s11033-012-2278-4. Epub 2013 Feb 11.
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.
多形性胶质母细胞瘤（GBM）被认为起源于 GBM 干细胞（GBM-SCs），是一种致命的脑肿瘤。microRNAs 对各种细胞过程进行转录后调控，从而调节 GBM-SCs 的干性特征。在这里，我们研究了 miR-153 在 GBM-SCs 中的关键作用。首先，我们从六个 GBM 标本中分离出 GBM-SCs。这些 GBM-SCs 形成 GBM 球体，表达与神经干细胞相关的标志物，具有自我更新和多谱系分化的能力。然后 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 CD133 阳性细胞中的表达相对于 CD133 阴性细胞下调。本项目首次证明，瞬时转染 miR-153 可以抑制 GBM-SCs 的干性特征，如削弱自我更新能力并诱导分化。同时，miR-153 还可以抑制 GBM-SCs 的生长并诱导细胞凋亡。总之，这些结果表明，重新激活 miR-153 的表达为 GBM-SCs 提供了新的治疗策略。
