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miR-143 inhibits glycolysis and depletes stemness of glioblastoma stem-like cells
Authors:Shiguang Zhao  Huailei Liu  Yaohua Liu  Jianing Wu  Chunlei Wang  Xu Hou  Xiaofeng Chen  Guang Yang  Ling Zhao  Hui Che  Yunke Bi  Hongyu Wang  Fei Peng  Jing Ai
Affiliation:1. Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province 150001, People’s Republic of China;2. Department of Internal Medicine, Heilongjiang International Travel Healthcare Center, Harbin, Heilongjiang Province, People’s Republic of China;3. Department of Pharmacology, State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Harbin Medical University, Harbin, Heilongjiang Province, People’s Republic of China
Abstract: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.
Keywords:miR-143   Glioblastoma stem-like cells   Glycolysis   Neurosphere   2-Deoxy-d-glucose (2-DG)
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