Oncogenic effects of miR-10b in glioblastoma stem cells.
Oncogenic effects of miR-10b in glioblastoma stem cells.
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miR-10b在胶质母细胞瘤干细胞中的致癌作用。
DOI：
10.1007/s11060-013-1047-0
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发表时间：
2013-04
影响因子：
3.9
通讯作者：
Abounader, Roger
中科院分区：
文献类型：
--
作者：
Guessous, Fadila;Alvarado-Velez, Melissa;Marcinkiewicz, Lukasz;Zhang, Ying;Kim, Jungeun;Heister, Simon;Kefas, Benjamin;Godlewski, Jakub;Schiff, David;Purow, Benjamin;Abounader, Roger
microrna和癌症干细胞在胶质母细胞瘤（最致命的人类癌症之一）中发挥了关键作用。在本研究中，我们研究了microRNA-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显示，胶质母细胞瘤患者的高miR-10b水平与预后不良之间存在相关性。我们测量了miR-10b的水平，发现与正常人类组织或星形胶质细胞相比，miR-10b在人类胶质母细胞瘤组织、胶质母细胞瘤细胞和干细胞系中上调。特异性拮抗剂抑制miR-10b抑制胶质母细胞瘤和干细胞系的增殖。抑制miR-10b可显著降低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可诱导细胞迁移和侵袭。我们还研究了miR-10b的几个预测靶点，但无法通过实验验证。此外，miR-10b抑制显著降低了干细胞来源的原位GBM异种移植物的体内生长。总之，我们的研究结果证实了miR-10b在GBM细胞中的致癌作用，并首次显示了该microRNA在GBM干细胞中的作用。因此，靶向miR-10b可能会抑制胶质母细胞瘤干细胞，胶质母细胞瘤干细胞被认为是胶质母细胞瘤的起源，并有助于其复发和对治疗的抵抗。
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.
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DOI：
10.4161/cc.9.6.10987
发表时间：
2010-03-15
期刊：
Cell cycle (Georgetown, Tex.)
影响因子：
--
作者：
Guessous F;Zhang Y;Kofman A;Catania A;Li Y;Schiff D;Purow B;Abounader R
通讯作者：
Abounader R
影响因子：
5.7
作者：
Chai, Guolin;Liu, Ning;Yu, Xijie
通讯作者：
Yu, Xijie
DOI：
10.4137/bcbcr.s8513
发表时间：
2012
期刊：
Breast cancer : basic and clinical research
影响因子：
--
作者：
Jin H;Yu Y;Chrisler WB;Xiong Y;Hu D;Lei C
通讯作者：
Lei C
影响因子：
11.2
作者：
Galli, R;Binda, E;Vescovi, A
通讯作者：
Vescovi, A
影响因子：
11.2
作者：
Gabriely G;Yi M;Narayan RS;Niers JM;Wurdinger T;Imitola J;Ligon KL;Kesari S;Esau C;Stephens RM;Tannous BA;Krichevsky AM
通讯作者：
Krichevsky AM