4.6 Article

VHL regulates the effects of miR-23b on glioma survival and invasion via suppression of HIF-1α/VEGF and β-catenin/Tcf-4 signaling

Journal

NEURO-ONCOLOGY
Volume 14, Issue 8, Pages 1026-1036

Publisher

OXFORD UNIV PRESS INC
DOI: 10.1093/neuonc/nos122

Keywords

glioma; HIF-1; microRNA; VHL; -catenin

Funding

  1. National High Technology Research and Development Program 863 [2012AA02A508]
  2. China National Natural Scientific Fund [30971136, 81001128, 81071044]
  3. Program for New Century Excellent Talents in University [NCET-07-0615]
  4. Tianjin Science and Technology Committee [09JCZDJC17600]

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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-1/VEGF expression and suppressed -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 -catenin/Tcf-4 and HIF-1/VEGF signaling pathways.

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