Abstract
BackgroundGlioma is the most common primary brain tumor in adults with a poor prognosis. As a member of ARF subfamily GTPase, ARL2 plays a key role in regulating the dynamics of microtubules and mitochondrial functions. Recently, ARL2 has been identified as a prognostic and therapeutic target in a variety range of malignant tumors. However, the biological functional role of ARL2 in glioma still remains unknown. The aim of this study was to explore the expression and functional role of ARL2 in glioma.MethodsIn this study, we investigated the expression of ARL2 in glioma samples by using RT-PCR, immunohistochemistry and western blot. The correlation between ARL2 expression and the outcomes of glioma patients was evaluated with survival data from TCGA, CGGA and Rembrandt dataset. Lentiviral technique was used for ARL2 overexpression in U87 and U251 cells. CCK8 assay, colony formation assay, wound healing test, transwell invasion assay and in vivo subcutaneous xenograft model were performed to investigated the biological functions of ARL2.ResultsARL2 expression was down-regulated in glioma, and was inversely associated with poor prognosis in glioma patients. Furthermore, exogenous ARL2 overexpression attenuated the growth and colony-formation abilities of glioma cells, as well as their migration and invasive capabilities. Moreover, elevated expression of ARL2 inhibited in vivo tumorigenicity of glioma cells. Mechanistically, ARL2 regulated AXL expression, which was known as an important functional regulator of proliferation and tumorigenicity in glioma cells.ConclusionOur study suggests that ARL2 inhibits the proliferation, migration and tumorigenicity of glioma cells by regulating the expression of AXL and may conduct as a new prognostic and therapeutic target for glioma.
Highlights
Glioma is the most common primary brain tumor in adults with a poor prognosis
ADP ribosylation factor-like GTPase 2 (ARL2) expression is decreased in glioma The expression of ARL family members in The Cancer Genome Atlas (TCGA) were studied through GlioVis, and ARL2 was significantly differentially expressed between glioma and non-tumor samples (Additional file 1: Figure S1)
Data from Sun (Additional file 2: Figure S2C, P < 0.001) and Griesinger dataset (Additional file 2: Figure S2D, P < 0.05) demonstrated the consistent results. These results demonstrated that ARL2 expression significantly decreased in glioma
Summary
Glioma is the most common primary brain tumor in adults with a poor prognosis. As a member of ARF subfamily GTPase, ARL2 plays a key role in regulating the dynamics of microtubules and mitochondrial functions. The aim of this study was to explore the expression and functional role of ARL2 in glioma. Glioma is the most common primary brain tumor in adults [1]. Recent studies have identified Ras mutations in some human carcinomas [6,7,8]. The mutated forms of KRAS-4B activate their downstream signaling cascades, and interact with each other and subsequently promote the proliferation of cancer cells and induce resistance to standard cancer therapies [6]
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