miR-143 inhibits glycolysis and depletes stemness of glioblastoma stem-like cells.

miR-143 inhibits glycolysis and depletes stemness of glioblastoma stem-like cells.
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miR-143 抑制糖酵解并消除胶质母细胞瘤干样细胞的干性。

DOI:
10.1016/j.canlet.2013.01.039
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发表时间:
2013-06
期刊:
影响因子:
9.7
通讯作者:
Ai J
Ai J
中科院分区:
医学1区
文献类型:
--
作者:
Bi Y;Wang H;Peng F;Ai J

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胶质母细胞瘤主要依靠有氧糖酵解来维持增殖和生长;然而,对胶质母细胞瘤干细胞中代谢的调控机制知之甚少。我们发现,miR-143在胶质瘤组织和胶质母细胞瘤干细胞样细胞(GSLCs)中显著下调,而miR-143过表达通过直接靶向己糖激酶2抑制糖酵解,并促进GSLCs的分化。此外,miR-143抑制GSLC在缺氧条件下的增殖,并降低GSLC体内肿瘤形成能力。我们还表明,miR-143和2-DG(一种广泛使用的糖酵解抑制剂)的组合对GSLC具有协同作用。miR-143是胶质母细胞瘤治疗的潜在治疗靶点。
Glioblastomas rely mainly on aerobic glycolysis to sustain proliferation and growth; however, little is known about the regulatory mechanisms of metabolism in glioblastoma stem cells. We show that miR-143 is significantly down-regulated in glioma tissues and glioblastoma stem-like cells (GSLCs), while miR-143 over-expression inhibits glycolysis by directly targeting hexokinase 2, and promotes differentiation of GSLCs. Moreover, miR-143 inhibits proliferation of GSLCs under hypoxic conditions and decreases tumor formation capacity of GSLCs in vivo. We also show that a combination of miR-143 and 2-DG, a widely used glycolysis inhibitor, has synergistic effects against GSLCs. miR-143 is a potential therapeutic target for glioblastoma treatment.
DOI: 10.4161/cc.9.6.10987
发表时间: 2010-03-15
期刊: Cell cycle (Georgetown, Tex.)
影响因子: --
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