Abstract
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.