AdipoR2 inhibits human glioblastoma cell growth through the AMPK/mTOR pathway
Chen Jie1, Wang Xuan2, Han-Dong Feng3
1Department of Neurosurgery, XuZhou Central Hospital, Xuzhou, China. SYSYS606@163.COM.
Background:
AdipoR2, which belongs to the seven-transmembrane-domain receptor family, has been shown to play an important role in the development of human tumours, but the underlying mechanisms are poorly understood. In this study, we found that AdipoR2 expression correlates with glioma grade. In addition, we also investigated the mechanisms behind the antiproliferative effects of AdipoR2 in U251 cells (a human glioma cell line) using colony formation and WST-8 growth assays.
Methods:
The U251 cell line was cultured in vitro. Western blotting was used to detect the expression of relevant proteins. Quantitative RT-PCR was used to detect AdipoR1 and AdipoR2 expression. Flow cytometry was used to detect cell cycle assay results. The gene expression profiles of glioma samples from the CGGA database were analysed by MATLAB and GSEA software.
Results:
The AMPK/mTOR pathway plays a central role in the regulation of cell proliferation, differentiation and migration and may promote tumorigenesis. Therefore, we can control cancer progression by modulating the AMPK/mTOR pathway. However, there is no information on the relationship between AdipoR and AMPK/mTOR in central nervous system tumours such as GBM. In this study. We found 648 upregulated genes and 436 downregulated genes correlated with AdipoR2 expression in 158 glioma samples. GSEA suggested that AdipoR2 is a cell cycle-associated gene. The results of the flow cytometry analysis indicated that AdipoR2 induced G0/G1 cell cycle arrest in U251 cells. Furthermore, we identified the AMPK/mTOR signalling axis to be involved in AdipoR2-induced cell cycle arrest.
Conclusions:
Our results suggest that AdipoR2 may represent a novel endogenous negative regulator of GBM cell proliferation. These findings also suggest that AdipoR2 may be a promising therapeutic target in GBM patients.
Insights
AdipoR2 expression correlates with glioma grade and inhibits cancer cell proliferation by inducing cell cycle arrest via the AMPK/mTOR pathway. This suggests AdipoR2 as a potential therapeutic target for glioblastoma multiforme (GBM).
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- AdipoR2, a seven-transmembrane-domain receptor, is implicated in human tumor development, but its precise mechanisms remain unclear.
- AdipoR2 expression levels were observed to correlate with glioma grade in this study.
- The study investigated the anti-proliferative mechanisms of AdipoR2 in U251 human glioma cells.
Purpose of the Study:
- To elucidate the role of AdipoR2 in glioma development and progression.
- To investigate the molecular mechanisms underlying AdipoR2's anti-proliferative effects in glioma cells.
- To explore the potential of AdipoR2 as a therapeutic target for glioblastoma.
Main Methods:
- Quantitative RT-PCR and Western blotting were used to assess AdipoR1 and AdipoR2 expression and protein levels.
- Colony formation and WST-8 assays evaluated the anti-proliferative effects of AdipoR2.
- Flow cytometry analyzed cell cycle distribution, while GSEA and MATLAB were used for gene expression profiling of glioma samples.
Main Results:
- AdipoR2 expression correlated with distinct gene expression profiles in 158 glioma samples, with 648 genes upregulated and 436 downregulated.
- Gene Set Enrichment Analysis (GSEA) indicated AdipoR2's association with cell cycle regulation.
- AdipoR2 induced G0/G1 cell cycle arrest in U251 cells, mediated by the AMPK/mTOR signaling pathway.
Conclusions:
- AdipoR2 acts as a novel endogenous negative regulator of glioblastoma multiforme (GBM) cell proliferation.
- AdipoR2's role in inducing cell cycle arrest via the AMPK/mTOR pathway presents it as a promising therapeutic target for GBM.
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