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：99

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

来源：

NEURO-ONCOLOGY | 2012年 / 14卷 / 08期

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 [肿瘤学];

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

页码：1026 / 1036

页数：11

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