Sirtuin 5 (SIRT5) 通过调节神经胶质瘤中的线粒体代谢和突触重塑来抑制肿瘤生长。
Sirtuin 5 (SIRT5) Suppresses Tumor Growth by Regulating Mitochondrial Metabolism and Synaptic Remodeling in Gliomas.
发表日期：2024 Aug 22
作者：
Wanjun Tang, Bo Chen, Gilberto Ka-Kit Leung, Karrie M Kiang
来源：
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
摘要：
Sirtuin 5 (SIRT5) 越来越被认为是细胞代谢的关键调节因子，癌细胞中细胞代谢通常失调，导致增殖增强和肿瘤进展。为了研究 SIRT5 失调在胶质母细胞瘤中的临床病理学意义，我们使用体外和体内胶质母细胞瘤模型对转录组数据和功能验证进行了全面分析。我们发现较高的 SIRT5 表达水平与神经胶质瘤患者的良好预后相关。 SIRT5 的敲低显着增强了胶质母细胞瘤细胞的生长。我们的数据表明它在调节神经胶质瘤线粒体代谢中的潜在作用。此外，SIRT5 还与突触重塑途径显着相关。我们的研究结果表明 SIRT5 的肿瘤抑制作用超出了调节癌症代谢的范围，它可能通过调节神经可塑性发挥作用。了解这些细胞相互作用可以帮助我们深入了解 SIRT5 的多方面作用以及其对开发新型治疗策略的更广泛的治疗意义。
Sirtuin 5 (SIRT5) is increasingly recognized as a key regulator of cellular metabolism, which is commonly dysregulated in cancer cells, resulting in enhanced proliferation and tumor progression. To investigate the clinicopathologic implications of SIRT5 dysregulation in glioblastoma, we performed comprehensive analyses of transcriptomic data and functional verifications using in vitro and in vivo glioblastoma models. We found that higher SIRT5 expression levels were associated with a favorable prognosis in glioma patients. Knockdown of SIRT5 significantly enhanced glioblastoma cell growth. Our data suggest its potential role in regulating mitochondrial metabolism in gliomas. Furthermore, SIRT5 is also significantly correlated with synaptic remodeling pathways. Our findings indicate a tumor-suppressive role for SIRT5 that extends beyond regulating cancer metabolism, by which it may function through modulating neuroplasticity. Understanding these cellular interactions provides nuanced insights into the multifaceted role of SIRT5 and the broader therapeutic implications of this for the development of novel treatment strategies.