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Published in: Journal of Neuro-Oncology 1/2018

01-10-2018 | Laboratory Investigation

RUNX3 inhibits glioma survival and invasion via suppression of the β-catenin/TCF-4 signaling pathway

Authors: Jikui Sun, Banban Li, Zhifan Jia, Anling Zhang, Guangxiu Wang, Zhijuan Chen, Zhende Shang, Chaocai Zhang, Jian Cui, Weidong Yang

Published in: Journal of Neuro-Oncology | Issue 1/2018

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Abstract

Introduction

Runt-related transcription factor 3 (RUNX3) exerts a tumor suppressor gene associated with gastric and other cancers, including glioma. However, how its anti-tumor mechanism in functions glioma is unclear.

Methods

We assayed expression of RUNX3 with a tissue microarray (TMA), frozen cancer tissues and malignant glioma cell lines using immunohistochemistry, qRT-PCR and Western bolt analysis. Cell proliferation, invasion, cell cycle distribution and apoptosis were also examined to confirm the effect of RUNX3 medicated malignant phenotype. TOP/FOP experiment was used to detect the β-catenin/Tcf-4 transcription activity by RUNX3.

Results

Enforced RUNX3 expression inhibited proliferation and invasion, induced cell cycle arrest and promoted apoptosis in vitro and in vivo, Bim siRNA partically reversed the effect of RUNX3-induced apoptosis in LN229 and U87 cells, suggesting a dependent role of Bim-caspase pathway. Moreover, Mechanism investigations revealed that restoration of RUNX3 suppressed β-catenin/Tcf-4 transcription activity.

Conclusions

RUNX3 plays a pivotal role in glioma initiation and progression as a tumor suppressor via attenuation of Wnt signaling, highlighting it as a potential therapeutic target for glioma.
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Metadata
Title
RUNX3 inhibits glioma survival and invasion via suppression of the β-catenin/TCF-4 signaling pathway
Authors
Jikui Sun
Banban Li
Zhifan Jia
Anling Zhang
Guangxiu Wang
Zhijuan Chen
Zhende Shang
Chaocai Zhang
Jian Cui
Weidong Yang
Publication date
01-10-2018
Publisher
Springer US
Published in
Journal of Neuro-Oncology / Issue 1/2018
Print ISSN: 0167-594X
Electronic ISSN: 1573-7373
DOI
https://doi.org/10.1007/s11060-018-2927-0

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