Overexpression of RASD1 inhibits glioma cell migration/invasion and inactivates the AKT/mTOR signaling pathway

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.

Undifferentiated Sarcomas Develop through Distinct Evolutionary Pathways

“…RASD1 , encoding a member of the RAS family, has a significantly reduced expression in rearranged samples (p = 5.9 × 10 −4 , q = 2.6 × 10 −3 ). In line with this observation, it has previously been proposed that RASD1 is a tumor suppressor gene in some cancer types (Gao et al., 2017). …”

Retracted: MicroRNA‐21 promotes glioma cell proliferation and inhibits senescence and apoptosis by targeting SPRY1 via the PTEN/PI3K/AKT signaling pathway

“…Due to its rapid expansion features, glioma activates cell migration and invades the normal brain, which indicates an unfavorable prognosis of patients with glioma like glioblastomas . The median survival time of patients with glioma after diagnosis remains to be only 1 year, in spite of advancements in available treatments such as surgery, radiotherapy, chemotherapy . It is known that the inhibition of tumor suppressor genes leads to gene methylation which further represses accumulation and induces mutation, which plays a significant role in the development and progression of tumor, and glioma progression is caused by an accumulation of epigenetic and genetic alterations …”

Undifferentiated Sarcomas Develop Through Distinct Evolutionary Pathways

“…RASD1, encoding a member of the RAS family, has a significantly reduced expression in rearranged samples (p = 5.9 3 10 À4 , q = 2.6 3 10 À3 ). In line with this observation, it has previously been proposed that RASD1 is a tumor suppressor gene in some cancer types (Gao et al, 2017).…”