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Journal of Neuro-Oncology

, Volume 140, Issue 1, pp 15–26 | Cite as

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

  • Jikui Sun
  • Banban Li
  • Zhifan Jia
  • Anling Zhang
  • Guangxiu Wang
  • Zhijuan Chen
  • Zhende Shang
  • Chaocai Zhang
  • Jian Cui
  • Weidong Yang
Laboratory Investigation
  • 157 Downloads

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.

Keywords

RUNX3 Glioma β-Catenin TCF-4 

Notes

Acknowledgements

This study was partially supported by National High Technology Research, the China National Natural Scientific Fund (81101915), Tai’an City Technology Development Project (2017NS0117), High Level Training Program of Taishan Medicine University (GCC16) and the China Scholarship Council.

Compliance with ethical standards

Conflict of interest

We confirm that there are potential conflict of interest associated with this publication. We also confirm that order of authors listed in the manuscript has been approved by all of us.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of NeurosurgeryAffiliated Hospital of Taishan Medical UniversityTaianPeople’s Republic of China
  2. 2.Life Science Research Centre of Taishan Medical UniversityTaianPeople’s Republic of China
  3. 3.Hematology departmentThe Central Hospital of TaianTaianPeople’s Republic of China
  4. 4.Department of NeurosurgeryTianjin Medical University General HospitalTianjinPeople’s Republic of China
  5. 5.Tianjin Neurological InstituteTianjinPeople’s Republic of China
  6. 6.Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous SystemMinistry of EducationTianjinPeople’s Republic of China
  7. 7.Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous SystemTianjinPeople’s Republic of China
  8. 8.Department of NeurosurgeryThe People Hospital of Hainan ProvinceHaikouPeople’s Republic of China
  9. 9.Oncology DepartmentThe Tumour Hospital of TaianTaianPeople’s Republic of China

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