Department of Neurosurgery, XuZhou Central Hospital, Xuzhou, China.
Xuzhou First People's Hospital, The Affiliated Hospital of China University of Mining and Technology, Xuzhou, China.
Eur J Med Res. 2021 Mar 22;26(1):28. doi: 10.1186/s40001-021-00496-9.
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.
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.
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.
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.
AdipoR2 属于七跨膜受体家族，已被证明在人类肿瘤的发展中发挥着重要作用，但潜在机制尚不清楚。在这项研究中，我们发现 AdipoR2 的表达与胶质瘤的分级相关。此外，我们还通过集落形成和 WST-8 生长测定研究了 AdipoR2 在 U251 细胞（一种人类神经胶质瘤细胞系）中抑制增殖的机制。
体外培养 U251 细胞系。Western blot 检测相关蛋白表达。定量 RT-PCR 检测 AdipoR1 和 AdipoR2 的表达。流式细胞术检测细胞周期试验结果。利用 MATLAB 和 GSEA 软件对 CGGA 数据库中胶质瘤样本的基因表达谱进行分析。
AMPK/mTOR 通路在调节细胞增殖、分化和迁移中起着核心作用，可能促进肿瘤发生。因此，我们可以通过调节 AMPK/mTOR 通路来控制癌症的进展。然而，在中枢神经系统肿瘤（如 GBM）中，AdipoR 与 AMPK/mTOR 之间的关系尚不清楚。在这项研究中，我们在 158 个胶质瘤样本中发现了与 AdipoR2 表达相关的 648 个上调基因和 436 个下调基因。GSEA 表明 AdipoR2 是一个与细胞周期相关的基因。流式细胞术分析结果表明，AdipoR2 诱导 U251 细胞发生 G0/G1 期细胞周期阻滞。此外，我们确定了 AMPK/mTOR 信号通路参与了 AdipoR2 诱导的细胞周期阻滞。
我们的研究结果表明，AdipoR2 可能代表了一种新型的胶质母细胞瘤细胞增殖的内源性负调控因子。这些发现也表明，AdipoR2 可能是胶质母细胞瘤患者有前途的治疗靶点。
