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ARL2 overexpression inhibits glioma proliferation and tumorigenicity via down-regulating AXL
Yulin Wang1, Gefei Guan1, Wen Cheng1
1Department of Neurosurgery, The First Hospital of China Medical University, 155 Nanjingbei Street, Heping, Shenyang, Liaoning, 110001, People's Republic of China.
Background:
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. 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.
Methods:
In 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.
Results:
ARL2 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.
Conclusion:
Our 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.
Insights
ARL2 (ADP-ribosylation factor like protein 2) is down-regulated in glioma, inhibiting tumor growth and spread. This finding suggests ARL2 could be a new therapeutic target for glioma patients.
Area of Science:
- Neuro-oncology
- Molecular Biology
- Cancer Research
Background:
- Glioma, a common adult brain tumor, has a poor prognosis.
- ARL2, an ARF subfamily GTPase, regulates microtubule dynamics and mitochondrial function.
- ARL2 is a potential prognostic and therapeutic target in various malignant tumors, but its role in glioma is unclear.
Purpose of the Study:
- To investigate the expression and functional role of ARL2 in glioma.
- To determine if ARL2 can serve as a prognostic or therapeutic target for glioma.
Main Methods:
- ARL2 expression analyzed via RT-PCR, immunohistochemistry, and Western blot in glioma samples.
- Patient outcomes correlated with ARL2 expression using TCGA, CGGA, and Rembrandt datasets.
- Functional roles assessed through cell proliferation, colony formation, migration, invasion assays, and in vivo xenograft models following ARL2 overexpression.
Main Results:
- ARL2 expression is downregulated in glioma and inversely associated with poor prognosis.
- Overexpression of ARL2 suppressed glioma cell proliferation, colony formation, migration, and invasion.
- Elevated ARL2 inhibited in vivo glioma cell tumorigenicity.
- ARL2 was found to regulate AXL expression, a key factor in glioma proliferation and tumorigenicity.
Conclusions:
- ARL2 inhibits glioma cell proliferation, migration, and tumorigenicity by regulating AXL expression.
- ARL2 presents potential as a novel prognostic and therapeutic target for glioma.
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