Abstract
MicroRNAs are a class of small noncoding RNAs that function as critical gene regulators through targeting mRNAs for translational repression or degradation. In this study, we showed that miR-128 expression levels were decreased in glioma, and identified p70S6K1 as a novel direct target of miR-128. Overexpression of miR-128 suppressed p70S6K1 and its downstream signaling molecules such as HIF-1 and VEGF expression, and attenuated cell proliferation, tumor growth and angiogenesis. Forced expression of p70S6K1 can partly rescue the inhibitory effect of miR-128 in the cells. Taken together, these findings will shed light to the role and mechanism of miR-128 in regulating glioma tumor angiogenesis via miR-128/p70S6K1 axis, and miR-128 may serve as a potential therapeutic target in glioma in the future.
Publication types
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Clinical Trial
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Line, Tumor
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Glioma / enzymology*
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Glioma / genetics
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Glioma / therapy
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Humans
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Hypoxia-Inducible Factor 1 / biosynthesis
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Hypoxia-Inducible Factor 1 / genetics
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Mice
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Mice, Inbred BALB C
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Mice, Nude
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MicroRNAs / biosynthesis*
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MicroRNAs / genetics
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Neoplasm Transplantation
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Neovascularization, Pathologic / enzymology*
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Neovascularization, Pathologic / genetics
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Neovascularization, Pathologic / therapy
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Ribosomal Protein S6 Kinases, 70-kDa / genetics
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Ribosomal Protein S6 Kinases, 70-kDa / metabolism*
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Signal Transduction / genetics
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Transplantation, Heterologous
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Vascular Endothelial Growth Factor A / biosynthesis
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Vascular Endothelial Growth Factor A / genetics
Substances
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Hypoxia-Inducible Factor 1
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MIRN128 microRNA, human
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MicroRNAs
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VEGFA protein, human
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Vascular Endothelial Growth Factor A
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Ribosomal Protein S6 Kinases, 70-kDa