Abstract
Aberrant microRNA expression has been implicated in the development of human cancers. Here, we investigated the oncogenic significance and function of miR-23b in glioma. We identified that the expression of miR-23b was elevated in both glioma samples and glioma cells, indicated by real-time polymerase chain reaction analyses. Down-regulation of miR-23b triggered growth inhibition, induced apoptosis, and suppressed invasion of glioma in vitro. Luciferase assay and Western blot analysis revealed that VHL is a direct target of miR-23b. Restoring expression of VHL inhibited glioma proliferation and invasion. Mechanistic investigation revealed that miR-23b deletion decreased HIF-1α/VEGF expression and suppressed β-catenin/Tcf-4 transcription activity by targeting VHL. Furthermore, expression of VHL was inversely correlated with miR-23b in glioma samples and was predictive of patient survival in a retrospective analysis. Therefore, we demonstrated that downregulation of miR-23b suppressed tumor survival through targeting VHL, leading to the inhibition of β-catenin/Tcf-4 and HIF-1α/VEGF signaling pathways.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / genetics
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Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / metabolism
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Blotting, Western
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Brain Neoplasms / genetics*
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Brain Neoplasms / metabolism
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Brain Neoplasms / pathology
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Cell Survival / genetics
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Enzyme-Linked Immunosorbent Assay
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Flow Cytometry
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Fluorescent Antibody Technique
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Gene Expression Regulation, Neoplastic / genetics*
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Glioma / genetics*
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Glioma / metabolism
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Glioma / pathology
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Humans
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Hypoxia-Inducible Factor 1, alpha Subunit / genetics
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Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
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Immunohistochemistry
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Mice
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MicroRNAs / genetics*
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MicroRNAs / metabolism
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Neoplasm Invasiveness / genetics
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Real-Time Polymerase Chain Reaction
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Signal Transduction / genetics*
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Transcription Factor 4
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Transcription Factors / genetics
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Transcription Factors / metabolism
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Transfection
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Transplantation, Heterologous
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Vascular Endothelial Growth Factor A / genetics
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Vascular Endothelial Growth Factor A / metabolism
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Von Hippel-Lindau Tumor Suppressor Protein / genetics*
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Von Hippel-Lindau Tumor Suppressor Protein / metabolism
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beta Catenin / genetics
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beta Catenin / metabolism
Substances
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Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
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CTNNB1 protein, human
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HIF1A protein, human
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Hypoxia-Inducible Factor 1, alpha Subunit
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MIRN23a microRNA, human
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MicroRNAs
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TCF4 protein, human
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Transcription Factor 4
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Transcription Factors
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Vascular Endothelial Growth Factor A
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beta Catenin
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Von Hippel-Lindau Tumor Suppressor Protein
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VHL protein, human