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

被引:68
|
作者
Zhao, Shiguang [1 ]
Liu, Huailei [1 ]
Liu, Yaohua [1 ]
Wu, Jianing [1 ]
Wang, Chunlei [1 ]
Hou, Xu [1 ]
Chen, Xiaofeng [1 ]
Yang, Guang [1 ]
Zhao, Ling [2 ]
Che, Hui [3 ]
Bi, Yunke [1 ]
Wang, Hongyu [1 ]
Peng, Fei [1 ]
Ai, Jing [3 ]
机构
[1] Harbin Med Univ, Affiliated Hosp 1, Dept Neurosurg, Harbin 150001, Heilongjiang Pr, Peoples R China
[2] Heilongjiang Int Travel Healthcare Ctr, Dept Internal Med, Harbin, Heilongjiang Pr, Peoples R China
[3] Harbin Med Univ, State Prov Key Labs Biomed Pharmaceut China, Dept Pharmacol, Harbin 150001, Heilongjiang Pr, Peoples R China
关键词
miR-143; Glioblastoma stem-like cells; Glycolysis; Neurosphere; 2-Deoxy-D-glucose (2-DG); HEXOKINASE; 2; HYPOXIA; 2-DEOXY-D-GLUCOSE; EXPRESSION; DIFFERENTIATION; CHEMORESISTANCE; RADIOTHERAPY; SUPPRESSION; INCREASES; GLIOMAS;
D O I
10.1016/j.canlet.2013.01.039
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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. (C) 2013 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:253 / 260
页数:8
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