Jikui Sun1,2,3,4, Banban Li5, Zhifan Jia3,4,6,7, Anling Zhang3,4,6,7, Guangxiu Wang3,4,6,7, Zhijuan Chen3,4,6,7, Zhende Shang1,2, Chaocai Zhang8, Jian Cui9, Weidong Yang10,11,12,13. 1. Department of Neurosurgery, Affiliated Hospital of Taishan Medical University, Taian, 271000, Shandong, People's Republic of China. 2. Life Science Research Centre of Taishan Medical University, Taian, 271000, Shandong, People's Republic of China. 3. Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, 300052, People's Republic of China. 4. Tianjin Neurological Institute, Tianjin, 300052, People's Republic of China. 5. Hematology department, The Central Hospital of Taian, Taian, 271000, Shandong, People's Republic of China. 6. Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin, 300052, People's Republic of China. 7. Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin, 300052, People's Republic of China. 8. Department of Neurosurgery, The People Hospital of Hainan Province, Haikou, 570311, People's Republic of China. 9. Oncology Department, The Tumour Hospital of Taian, Taian, 271000, Shandong, People's Republic of China. 10. Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, 300052, People's Republic of China. weidongyang16@163.com. 11. Tianjin Neurological Institute, Tianjin, 300052, People's Republic of China. weidongyang16@163.com. 12. Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin, 300052, People's Republic of China. weidongyang16@163.com. 13. Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin, 300052, People's Republic of China. weidongyang16@163.com.
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.
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.
Authors: Jun Xue; Xueliang Wu; Ming Qu; Fei Guo; Lei Han; Guangyuan Sun; Zelong Yuan; Shuang Fan; Tian Li Journal: Evid Based Complement Alternat Med Date: 2020-02-27 Impact factor: 2.629