Sirt3 enhances glioma cell viability by stabilizing Ku70–BAX interaction

Ke Luo,* Wei Huang,* Shuang Tang Department of Neurosurgery, Suining Central Hospital, Suining, Sichuan, China *These authors contributed equally to this work Background: 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. Methods: 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. Results: Sirt3 expression was lower in glioma tissues than normal brain tissues. Higher Sirt3 is significantly correlated to advanced tumor grade (P=0.004), showing its potential role in cancer progression. Consistently, univariate and multivariate analyses identified Sirt3 as an independent prognostic factor (P=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. Conclusion: 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. Keywords: glioma, prognosis, Sirt3, viabilit