Abstract
The RAS signaling pathway is hyperactive in malignant glioma due to overexpression and/or increased activity. A previous study identified that RASD1, a member of the RAS superfamily of small G-proteins, is a significantly dysregulated gene in oligodendroglial tumors that responded to chemotherapy. However, the role and mechanism of RASD1 in the progression of human glioma remain largely unknown. In the present study, by analyzing a public genomics database, we found that high levels of RASD1 predicted good survival of astrocytoma patients. We thus established lentivirus-mediated RASD1-overexpressing glioma cells and found that overexpressing RASD1 had no significant effects on glioma cell proliferation. However, the overexpression of RASD1 inhibited glioma cell migration and invasion. In the intracranial glioma xenograft model, the overexpression of RASD1 significantly reduced the number of tumor cells invading into the surrounding tissues without affecting the tumor size. An intracellular signaling array revealed that the phosphorylation of both AKT and the S6 ribosomal protein significantly decreased with RASD1 overexpression in glioma cells. Interestingly, RASD1 protein levels were significantly higher in grade II and grade III astrocytoma tissues than in nontumorous brain tissues. These findings suggest that the upregulation of RASD1 in glioma tissues may play an inhibitory role in tumor expansion, possibly through inactivating the AKT/mTOR signaling pathway.
Highlights
Glioma is the most common and aggressive primary brain tumor
We demonstrated that the overexpression of RASD1 significantly inhibited the migration and invasion of glioma cells, without affecting cell proliferation
A significantly positive association of RASD1 levels with the overall survival of astrocytoma patients was found by analyzing a public database
Summary
Glioma is the most common and aggressive primary brain tumor. Despite the advances in surgery and adjuvant therapy, the median survival of glioblastoma patients is only 1 year[1, 2]. RASD1, named Dexras[1] or AGS1, is a member of the RAS superfamily of small G-proteins[6], which plays important roles in tumor growth and expansion. It was first discovered as a dexamethasone-inducible cDNA in mouse corticotroph cells ( the name Dexras1)[7] and subsequently as a receptor-independent activator of heterotrimeric G-protein signaling ( the name AGS1)[8]. That RASD1, a member of the RAS superfamily of small G-proteins that often promotes cell growth and tumor expansion[3,4,5], may play an active role in preventing aberrant cell growth. These clinical data suggested the potential involvement of RASD1 in the progression of human glioma
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
