Department of Pharmacy, Huashan Hospital, Fudan University, Shanghai, China.
Department of Anesthesiology, Huashan Hospital, Fudan University, Shanghai, China.
Biomol Biomed. 2024 Oct 17;24(6):1620-1636. doi: 10.17305/bb.2024.10443.
Small Ubiquitin-like Modifier (SUMOylation) regulates a variety of cellular activities, and its dysregulation has been associated with glioma etiology. The aim of this research was to clarify the function of SUMOylation-related genes in glioma and determine relevant prognostic markers. The Cancer Genome Atlas (TCGA) Glioma and GSE16011 datasets were analyzed through bioinformatics to identify Ran GTPase activating protein 1 (RANGAP1) as the hub gene for further study. Experimental validation consisted of quantitative real-time polymerase chain reaction (qRT-PCR), western blotting (WB), and immunoprecipitation (IP) to evaluate RANGAP1 expression, function, and interaction with SUMO1. To assess the role of RANGAP1 knockdown and SUMOylation in glioma cells, various assays were conducted, including cell proliferation, migration, invasion, and apoptosis. In addition, cell cycle analysis and immunofluorescence were performed. Through bioinformatics, RANGAP1 was identified as a crucial prognostic gene for glioma. Experimental studies confirmed the downregulation of RANGAP1 in glioma cells and verified that RANGAP1 repair impedes tumor growth. When it comes to RANGAP1 silencing, it enhanced cell proliferation, invasion and migration. Additionally, SUMO1 was identified as a specific SUMO molecule coupled to RANGAP1, affecting the location of Sma and Mad related protein 4 (Smad4) in the nucleocytoplasm and the transforming growth factor (TGF)-β/Smad signaling pathway. The functional impact of RANGAP1 SUMOylation on cell proliferation and migration was further confirmed through experiments using a SUMOylation-impairing mutation (K524R). Our findings suggest that RANGAP1 may be a potential prognostic marker in gliomas and could play a role in regulating cell proliferation, migration, and invasion. SUMOylation of RANGAP1 is responsible for regulating the TGF-β/Smad signaling pathway, which is crucial for the progression of tumors. Further investigations and experiments are necessary to confirm these results.
小泛素样修饰物（SUMOylation）调节多种细胞活动，其失调与神经胶质瘤的病因有关。本研究旨在阐明 SUMOylation 相关基因在神经胶质瘤中的功能，并确定相关的预后标志物。通过生物信息学分析癌症基因组图谱（TCGA）神经胶质瘤和 GSE16011 数据集，确定 Ran GTPase 激活蛋白 1（RANGAP1）为进一步研究的枢纽基因。实验验证包括定量实时聚合酶链反应（qRT-PCR）、蛋白质印迹（WB）和免疫沉淀（IP），以评估 RANGAP1 的表达、功能以及与 SUMO1 的相互作用。为了评估 RANGAP1 敲低和 SUMOylation 在神经胶质瘤细胞中的作用，进行了各种实验，包括细胞增殖、迁移、侵袭和凋亡。此外，还进行了细胞周期分析和免疫荧光实验。通过生物信息学分析，确定 RANGAP1 是神经胶质瘤的一个关键预后基因。实验研究证实了 RANGAP1 在神经胶质瘤细胞中的下调，并验证了 RANGAP1 修复阻碍肿瘤生长。当 RANGAP1 沉默时，它增强了细胞增殖、侵袭和迁移。此外，确定 SUMO1 是与 RANGAP1 结合的特定 SUMO 分子，影响 Smad 相关蛋白 4（Smad4）在核质中的位置和转化生长因子（TGF）-β/Smad 信号通路。通过使用 SUMOylation 损伤突变（K524R）的实验进一步证实了 RANGAP1 SUMOylation 对细胞增殖和迁移的功能影响。我们的研究结果表明，RANGAP1 可能是神经胶质瘤的一个潜在预后标志物，可能在调节细胞增殖、迁移和侵袭方面发挥作用。RANGAP1 的 SUMOylation 负责调节 TGF-β/Smad 信号通路，这对肿瘤的进展至关重要。需要进一步的研究和实验来证实这些结果。
