Department of Surgery, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong.
State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong.
Int J Mol Sci. 2024 Aug 22;25(16):9125. doi: 10.3390/ijms25169125.
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.
Sirtuin 5（SIRT5）被越来越多地认为是细胞代谢的关键调节剂，在癌细胞中通常失调，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意义，我们使用体外和体内胶质母细胞瘤模型进行了转录组数据的综合分析和功能验证。我们发现，SIRT5 表达水平较高与胶质瘤患者的预后良好相关。SIRT5 的敲低显著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胶质瘤中的线粒体代谢中具有潜在作用。此外，SIRT5 还与突触重塑途径显著相关。我们的研究结果表明，SIRT5 具有肿瘤抑制作用，其作用不仅局限于调节癌症代谢，还可以通过调节神经可塑性来发挥作用。了解这些细胞间的相互作用为 SIRT5 的多方面作用提供了细微的见解，也为开发新的治疗策略提供了更广泛的治疗意义。
