DLGAP3 suppresses malignant behaviors of glioma cells via inhibiting RGS12-mediated MAPK/ERK signaling

[Display omitted] •DLGAP3 functions as a tumor suppressor and a prognostic marker in glioma.•Low expressed DLGAP3 in gliomas predicts poor survival of glioma patients.•DLGAP3 dramatically inhibits biological malignant behaviors of glioma cells.•DLGAP3 suppresses MAPK/ERK signaling in glioma cells by regulating RGS12. 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. 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. 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. Our data indicates that DLGAP3 is a potential tumor suppressor and valuable prognostic biomarker in gliomas.