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

Lingchao Chen, Lei Han, Kailiang Zhang, Zhendong Shi, Junxia Zhang, Anling Zhang, Yongzhi Wang, Yijun Song, Yongli Li, Tao Jiang, Peiyu Pu, Chuanlu Jiang, Chunsheng Kang
Neuro-oncology 2012, 14 (8): 1026-36
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.

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