Jing Wei, Yuan Li, Fangzheng Jiao, Xiaoya Wang, Han Zhou, Yifan Qiao, Zihan Yuan, Chao Qian, Yanlong Tian, Yan Fang
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引用次数: 0
Abstract
Background: Glioma is the most common malignant tumor of the central nervous system, and is characterized by high recurrence, poor prognosis and especially complex pathogenesis. The synaptic plasticity-related protein DLGAP3 is mainly involved in the assembly and function of postsynaptic density complex. It's widely known that DLGAP3 participating in the occurrence of various neuropsychiatric diseases, but its role in glioma tumorigenesis remains largely unclear.
Methods: We ectopically expressed and knocked down DLGAP3 in glioma cells to perform a series of functional studies in vitro. Meanwhile, western blot analysis, co-immunoprecipitation, enrichment analysis and dual-luciferase reporter system assays were performed to explore the mechanism of DLGAP3 suppressing glioma tumorigenesis and progression.
Results: We found that DLGAP3 was low expressed in gliomas, and decreased DLGAP3 expression was strongly correlated with poor survival of glioma patients. Ectopic expression of DLGAP3 in glioma cell lines dramatically inhibited cell proliferation, invasion and migration. In addition, our data also showed that DLGAP3 can tightly connected with RGS12, and DLGAP3 overexpression significantly increased the expression of RGS12 and inhibited the phosphorylation levels of MEK and ERK. Furthermore, the RGS12 inhibited transcription and translation of BRAF, which further decreased the activity of MAPK/ERK signaling pathway. This suggests that DLGAP3 may act as a tumor suppressor in gliomas and inhibits glioma tumorigenesis by regulating RGS12 and the downstream MAPK/ERK signals axis.
Conclusion: Our data indicates that DLGAP3 is a potential tumor suppressor and valuable prognostic biomarker in gliomas.
期刊介绍：
An international multidisciplinary journal devoted to fundamental research in the brain sciences.
Brain Research publishes papers reporting interdisciplinary investigations of nervous system structure and function that are of general interest to the international community of neuroscientists. As is evident from the journals name, its scope is broad, ranging from cellular and molecular studies through systems neuroscience, cognition and disease. Invited reviews are also published; suggestions for and inquiries about potential reviews are welcomed.
With the appearance of the final issue of the 2011 subscription, Vol. 67/1-2 (24 June 2011), Brain Research Reviews has ceased publication as a distinct journal separate from Brain Research. Review articles accepted for Brain Research are now published in that journal.
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