Long Hai1,2,3,4, Peidong Liu2, Shengping Yu2, Li Yi2, Zhennan Tao2, Chen Zhang5,6, Iruni Roshanie Abeysekera7, Tao Li2, Luqing Tong2, Haiwen Ma2, Bo Liu2, Yang Xie2, Xingchen Zhou2, Yu Lin2, Meng Zhu5, Kai Zhang2, Bingcheng Ren2, Haolang Ming2, Yubao Huang2, Xuejun Yang8,9,10. 1. Department of Radiation Oncology, Henan Cancer Hospital, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China. 2. Department of Neurosurgery, Tianjin Medical University General Hospital, Laboratory of Neuro-Oncology, Tianjin Neurological Institute, Tianjin, China. 3. Key Laboratory of Post-trauma Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin, China. 4. Chinese Glioma Cooperative Group (CGCG), Beijing, China. 5. Department of Neurosurgery, The Affiliated Hospital of Qingdao University, Qingdao, China. 6. Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. 7. Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin, China. 8. Department of Neurosurgery, Tianjin Medical University General Hospital, Laboratory of Neuro-Oncology, Tianjin Neurological Institute, Tianjin, Chinaydenny@126.com. 9. Key Laboratory of Post-trauma Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin, Chinaydenny@126.com. 10. Chinese Glioma Cooperative Group (CGCG), Beijing, Chinaydenny@126.com.
Abstract
BACKGROUND/AIMS: Jagged1 is the ligands of the Notch signaling and has been shown to promote glioma-initiating cells (GICs) in glioblastoma. The role of Jagged1 in GICs invasion and underlying molecular mechanisms remain unclear. METHODS: Survival data from R2 genomics analysis, the Cancer Genome Atlas (TCGA), the Chinese Glioma Genome Atlas (CGGA) and visualization platform database were used to evaluate the effects of Jagged1 on overall patient survival. we investigated Jagged1 induced the GICs cells' invasion by matrix degradation assays and Transwell cell invasion assays in vitro, then we further explored the underlying molecular mechanisms using Co-immunoprecipitation (co-IP) analysis. RESULTS: High expression of Jagged1 in human glioma was associated with poor survival. Clinical data analysis showed that the Jagged1 was positively correlated with NF-κB(p65). Jagged1-induced invasion of GICs cells through activation of NF-κB(p65) pathway. In vivo, knockdown of Jagged1 could suppress the tumorigenicity of GICs cells through NF-κB(p65) signaling. CONCLUSION: Insights gained from these findings suggest that Jagged1 plays an important oncogenic role in GICs malignancy by activation of NF-κB(p65) signaling, and Jagged1 could be employed as an effective therapeutic target for GICs.
BACKGROUND/AIMS: Jagged1 is the ligands of the Notch signaling and has been shown to promote glioma-initiating cells (GICs) in glioblastoma. The role of Jagged1 in GICs invasion and underlying molecular mechanisms remain unclear. METHODS: Survival data from R2 genomics analysis, the Cancer Genome Atlas (TCGA), the Chinese Glioma Genome Atlas (CGGA) and visualization platform database were used to evaluate the effects of Jagged1 on overall patient survival. we investigated Jagged1 induced the GICs cells' invasion by matrix degradation assays and Transwell cell invasion assays in vitro, then we further explored the underlying molecular mechanisms using Co-immunoprecipitation (co-IP) analysis. RESULTS: High expression of Jagged1 in humanglioma was associated with poor survival. Clinical data analysis showed that the Jagged1 was positively correlated with NF-κB(p65). Jagged1-induced invasion of GICs cells through activation of NF-κB(p65) pathway. In vivo, knockdown of Jagged1 could suppress the tumorigenicity of GICs cells through NF-κB(p65) signaling. CONCLUSION: Insights gained from these findings suggest that Jagged1 plays an important oncogenic role in GICs malignancy by activation of NF-κB(p65) signaling, and Jagged1 could be employed as an effective therapeutic target for GICs.