Departments of Microbiology, Immunology and Cancer Biology, University of Virginia, Charlottesville, VA 22908, USA.
J Neurooncol. 2013 Apr;112(2):153-63. doi: 10.1007/s11060-013-1047-0. Epub 2013 Jan 10.
MicroRNAs and cancer stem cells have emerged as critical players in glioblastoma, one of the deadliest human cancers. In this study, we investigated the expression and function of microRNA-10b in glioblastoma cells and stem cells. An analysis of The Cancer Genome Atlas data revealed a correlation between high miR-10b levels and poor prognosis in glioblastoma patients. We measured the levels of miR-10b and found that it is upregulated in human glioblastoma tissues, glioblastoma cell and stem cell lines as compared to normal human tissues or astrocytes. Inhibition of miR-10b with a specific antagomir inhibited the proliferation of glioblastoma established and stem cell lines. Inhibition of miR-10b strongly reduced cell invasion and migration in glioblastoma cell and stem cell lines while overexpression of miR-10b induced cell migration and invasion. We also investigated several predicted targets of miR-10b but could not verify any of them experimentally. Additionally, miR-10b inhibition significantly decreased the in vivo growth of stem cell-derived orthotopic GBM xenografts. Altogether, our findings confirm the oncogenic effects of miR-10b in GBM cells and show for the first time a role of this microRNA in GBM stem cells. Targeting miR-10b might therefore inhibit glioblastoma stem cells, which are thought to be at the origin of glioblastoma and to contribute its recurrence and resistance to therapy.
微小 RNA 和癌症干细胞已成为胶质母细胞瘤（一种最致命的人类癌症）的关键参与者。在这项研究中，我们研究了微小 RNA-10b 在胶质母细胞瘤细胞和干细胞中的表达和功能。对癌症基因组图谱数据的分析表明，miR-10b 水平高与胶质母细胞瘤患者预后不良相关。我们测量了 miR-10b 的水平，发现它在人胶质母细胞瘤组织、胶质母细胞瘤细胞和干细胞系中上调，与正常人组织或星形胶质细胞相比。用特异性反义寡核苷酸抑制 miR-10b 抑制了已建立的胶质母细胞瘤和干细胞系的增殖。抑制 miR-10b 强烈降低了胶质母细胞瘤细胞和干细胞系的细胞侵袭和迁移，而过表达 miR-10b 诱导了细胞迁移和侵袭。我们还研究了 miR-10b 的几个预测靶标，但未能在实验中验证任何一个。此外，miR-10b 抑制显著减少了干细胞源性原位 GBM 异种移植的体内生长。总之，我们的研究结果证实了 miR-10b 在 GBM 细胞中的致癌作用，并首次表明这种 microRNA 在 GBM 干细胞中发挥作用。因此，靶向 miR-10b 可能抑制被认为是胶质母细胞瘤起源并导致其复发和对治疗产生耐药性的胶质母细胞瘤干细胞。
