Luo Ke, Huang Wei, Tang Shuang
Department of Neurosurgery, Suining Central Hospital, Suining, Sichuan, China,
Onco Targets Ther. 2018 Oct 29;11:7559-7567. doi: 10.2147/OTT.S172672. eCollection 2018.
As one of the most prevalent malignancies, glioma is characterized by poor prognosis and high mortality rate. Glioma patients may show completely distinct clinical outcomes due to their different molecular patterns. Sirtuin 3 (Sirt3) participates in aging, stress resistance, and metabolic regulation. Here we aimed to test the expression and function of Sirt3 in glioma.
We enrolled 114 patients and tested the protein level of Sirt3 in their glioma tissues. The correlation between prognosis and Sirt3 was evaluated by univariate and multivariate analyses. We also conducted cellular experiments in U87 and U251 glioma cells, including overexpression and knockdown assays.
Sirt3 expression was lower in glioma tissues than normal brain tissues. Higher Sirt3 is significantly correlated to advanced tumor grade (=0.004), showing its potential role in cancer progression. Consistently, univariate and multivariate analyses identified Sirt3 as an independent prognostic factor (=0.017). Patients with higher Sirt3 expression showed significantly shorter overall survival time. Moreover, overexpression of Sirt3 in either cell line enhanced cell viability, while silencing Sirt3 attenuated cell growth. Molecular assays showed Sirt3 can deacetylate Ku70 protein, therefore stabilizing the Ku70-BAX interaction. Since Ku70 can help prevent BAX transporting into mitochondria and decrease cell apoptosis, Sirt3 protein may play roles in maintaining cell viability. In addition, silencing Ku70 inhibited the pro-proliferative effect by Sirt3.
Taken together, our results not only identified the prognostic role of Sirt3 in glioma patients but also provided signaling pathway evidence for its functioning mechanisms.
作为最常见的恶性肿瘤之一，胶质瘤的特点是预后差和死亡率高。由于分子模式不同，胶质瘤患者可能表现出完全不同的临床结果。沉默调节蛋白3（Sirt3）参与衰老、抗应激和代谢调节。在此，我们旨在检测Sirt3在胶质瘤中的表达和功能。
我们招募了114例患者，检测了他们胶质瘤组织中Sirt3的蛋白水平。通过单因素和多因素分析评估预后与Sirt3之间的相关性。我们还在U87和U251胶质瘤细胞中进行了细胞实验，包括过表达和敲低实验。
胶质瘤组织中Sirt3的表达低于正常脑组织。较高的Sirt3与肿瘤高级别显著相关（P = 0.004），表明其在癌症进展中的潜在作用。同样，单因素和多因素分析确定Sirt3为独立的预后因素（P = 0.017）。Sirt3表达较高的患者总生存时间明显较短。此外，在任一细胞系中过表达Sirt3均可增强细胞活力，而沉默Sirt3则减弱细胞生长。分子检测表明Sirt3可使Ku70蛋白去乙酰化，从而稳定Ku70 - BAX相互作用。由于Ku70可帮助防止BAX转运至线粒体并减少细胞凋亡，Sirt3蛋白可能在维持细胞活力中发挥作用。此外，沉默Ku70可抑制Sirt3的促增殖作用。
综上所述，我们的结果不仅确定了Sirt3在胶质瘤患者中的预后作用，还为其作用机制提供了信号通路证据。
