JOURNAL/nrgr/04.03/01300535-202504000-00029/figure1/v/2024-07-06T104127Z/r/image-tiff 最近的研究证明了体力活动对神经胶质瘤患者预后的影响，有证据表明运动可以降低死亡率风险并帮助神经再生。小泛素样修饰剂 (SUMO) 蛋白（尤其是运动后）在癌症进展中的作用越来越受到关注，SUMO 化的潜在抗癌作用也越来越受到关注。我们使用机器学习来创建练习和 SUMO 相关基因签名 (ESLRS)。这一特征表明体力活动如何有助于改善低级别神经胶质瘤和其他癌症的前景。我们证明了 ESLRS 标记物的预后和免疫治疗意义，特别强调了 nutlin-3 如何靶向小鼠双微体 2 (MDM2)（ESLRS 的一个组成部分）。这强调了 nutlin-3 等天然化合物与免疫调节之间的复杂关系。通过全面的 CRISPR 筛选，我们验证了特定 ESLRS 基因对低级别胶质瘤进展的影响。我们还通过分子对接和动态模拟揭示了 Nutlin-3a 作为有效 MDM2 抑制剂有效性的见解。 Nutlin-3a 抑制神经胶质瘤细胞增殖并激活 p53 通路。其功效随着 MDM2 过度表达而降低，而 Nutlin-3a 或运动可以逆转这种情况。使用低级别神经胶质瘤小鼠模型的实验强调了体力活动对氧化应激和分子途径调节的影响。值得注意的是，体育锻炼和 Nutlin-3a 给药均可改善携带源自 MDM2 过表达细胞的肿瘤的小鼠的身体功能。这些结果表明 Nutlin-3a（一种 MDM2 抑制剂）通过体育锻炼作为神经胶质瘤治疗方法的潜力。我们的研究还支持使用天然产品进行治疗，并揭示了运动、天然产品和免疫调节在癌症治疗中的相互作用。版权所有 © 2025 版权所有：© 2025 神经再生研究。

JOURNAL/nrgr/04.03/01300535-202504000-00029/figure1/v/2024-07-06T104127Z/r/image-tiff Recent research has demonstrated the impact of physical activity on the prognosis of glioma patients, with evidence suggesting exercise may reduce mortality risks and aid neural regeneration. The role of the small ubiquitin-like modifier (SUMO) protein, especially post-exercise, in cancer progression, is gaining attention, as are the potential anti-cancer effects of SUMOylation. We used machine learning to create the exercise and SUMO-related gene signature (ESLRS). This signature shows how physical activity might help improve the outlook for low-grade glioma and other cancers. We demonstrated the prognostic and immunotherapeutic significance of ESLRS markers, specifically highlighting how murine double minute 2 (MDM2), a component of the ESLRS, can be targeted by nutlin-3. This underscores the intricate relationship between natural compounds such as nutlin-3 and immune regulation. Using comprehensive CRISPR screening, we validated the effects of specific ESLRS genes on low-grade glioma progression. We also revealed insights into the effectiveness of Nutlin-3a as a potent MDM2 inhibitor through molecular docking and dynamic simulation. Nutlin-3a inhibited glioma cell proliferation and activated the p53 pathway. Its efficacy decreased with MDM2 overexpression, and this was reversed by Nutlin-3a or exercise. Experiments using a low-grade glioma mouse model highlighted the effect of physical activity on oxidative stress and molecular pathway regulation. Notably, both physical exercise and Nutlin-3a administration improved physical function in mice bearing tumors derived from MDM2-overexpressing cells. These results suggest the potential for Nutlin-3a, an MDM2 inhibitor, with physical exercise as a therapeutic approach for glioma management. Our research also supports the use of natural products for therapy and sheds light on the interaction of exercise, natural products, and immune regulation in cancer treatment.Copyright © 2025 Copyright: © 2025 Neural Regeneration Research.