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

被引:92
作者
Chen, Lingchao [3 ]
Han, Lei [1 ,2 ]
Zhang, Kailiang [1 ,2 ]
Shi, Zhendong [1 ,2 ]
Zhang, Junxia [1 ,2 ]
Zhang, Anling [1 ,2 ]
Wang, Yongzhi [4 ]
Song, Yijun [5 ]
Li, Yongli [3 ]
Jiang, Tao [4 ]
Pu, Peiyu [1 ,2 ]
Jiang, Chuanlu [3 ]
Kang, Chunsheng [1 ,2 ]
机构
[1] Tianjin Med Univ, Dept Neurosurg, Gen Hosp, Lab Neurooncol,Tianjin Neurol Inst, Tianjin, Peoples R China
[2] Minist Educ & Tianjin Municipal Govt, Key Lab Neurotrauma Variat & Regenerat, Tianjin, Peoples R China
[3] Harbin Med Univ, Dept Neurosurg, Affiliated Hosp 2, Harbin, Peoples R China
[4] Capital Med Univ, Dept Neurosurg, Tiantan Hosp, Beijing, Peoples R China
[5] Tianjin Med Univ, Dept Neurol, Gen Hosp, Tianjin, Peoples R China
关键词
glioma; HIF-1; microRNA; VHL; -catenin; TUMOR-SUPPRESSOR; MALIGNANT GLIOMA; DOWN-REGULATION; BETA-CATENIN; GLIOBLASTOMA; GROWTH; CELLS; THERAPY; PATHWAY; CANCER;
D O I
10.1093/neuonc/nos122
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:1026 / 1036
页数:11
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