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

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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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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.

Author information

Author notes

  1. Jikui Sun, Banban Li, and Zhifan Jia contributed equally to this work.

Authors and Affiliations

  1. Department of Neurosurgery, Affiliated Hospital of Taishan Medical University, Taian, 271000, Shandong, People’s Republic of China

    Jikui Sun & Zhende Shang

  2. Life Science Research Centre of Taishan Medical University, Taian, 271000, Shandong, People’s Republic of China

    Jikui Sun & Zhende Shang

  3. Hematology department, The Central Hospital of Taian, Taian, 271000, Shandong, People’s Republic of China

    Banban Li

  4. Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, 300052, People’s Republic of China

    Jikui Sun, Zhifan Jia, Anling Zhang, Guangxiu Wang, Zhijuan Chen & Weidong Yang

  5. Tianjin Neurological Institute, Tianjin, 300052, People’s Republic of China

    Jikui Sun, Zhifan Jia, Anling Zhang, Guangxiu Wang, Zhijuan Chen & Weidong Yang

  6. Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin, 300052, People’s Republic of China

    Zhifan Jia, Anling Zhang, Guangxiu Wang, Zhijuan Chen & Weidong Yang

  7. Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin, 300052, People’s Republic of China

    Zhifan Jia, Anling Zhang, Guangxiu Wang, Zhijuan Chen & Weidong Yang

  8. Department of Neurosurgery, The People Hospital of Hainan Province, Haikou, 570311, People’s Republic of China

    Chaocai Zhang

  9. Oncology Department, The Tumour Hospital of Taian, Taian, 271000, Shandong, People’s Republic of China

    Jian Cui

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  1. Jikui Sun
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  2. Banban Li
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Correspondence to Weidong Yang.

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Sun, J., Li, B., Jia, Z. et al. RUNX3 inhibits glioma survival and invasion via suppression of the β-catenin/TCF-4 signaling pathway. J Neurooncol 140, 15–26 (2018). https://doi.org/10.1007/s11060-018-2927-0

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  • DOI: https://doi.org/10.1007/s11060-018-2927-0

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