Department of Biochemistry and Molecular Biology, GMU-GIBH Joint School of Life Sciences, Guangzhou Medical University, Guangzhou, 510182, People's Republic of China.
State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, People's Republic of China.
Cell Commun Signal. 2018 Jun 11;16(1):28. doi: 10.1186/s12964-018-0240-3.
SOD1 is an abundant enzyme that has been studied as a regulator of the antioxidant defence system, and this enzyme is well known for catalyzing the dismutation of superoxide into hydrogen peroxide. However the SOD1 in the progress of NPC and underlying mechanisms remain unclear.
In NPC tissue samples, SOD1 protein levels were measured by Western blot and immunohistochemical (IHC) staining. mRNA levels and SOD1 activity were monitored by qRT-PCR and SOD activity kit, respectively. Kaplan-Meier survival analysis was performed to explore the relationship between SOD1 expression and prognosis of NPC. The biological effects of SOD1 were investigated both in vitro by CCK-8, clonogenicity and apoptosis assays and in vivo by a xenograft mice model. Western blotting, ROS assay and triglyceride assays were applied to investigate the underlying molecular mechanism of pro-survival role of SOD1 in NPC.
We observed a significant upregulation of SOD1 in NPC tissue and high SOD1 expression is a predictor of poor prognosis and is correlated with poor outcome. We confirmed the pro-survival role of SOD1 both in vitro and in vivo. We demonstrated that these mechanisms of SOD1 partly exist to maintain low levels of the superoxide anion and to avoid the accumulation of lipid droplets via enhanced CPT1A-mediated fatty acid oxidation.
The results of this study indicate that SOD1 is a potential prognostic biomarker and a promising target for NPC therapy.
SOD1 是一种丰富的酶，它被研究为抗氧化防御系统的调节剂，该酶以催化超氧化物歧化为过氧化氢而闻名。然而，NPC 进展中的 SOD1 及其潜在机制仍不清楚。
在 NPC 组织样本中，通过 Western blot 和免疫组织化学（IHC）染色来测量 SOD1 蛋白水平。通过 qRT-PCR 和 SOD 活性试剂盒分别监测 mRNA 水平和 SOD1 活性。进行 Kaplan-Meier 生存分析以探索 SOD1 表达与 NPC 预后之间的关系。通过 CCK-8、集落形成和细胞凋亡测定法在体外以及通过异种移植小鼠模型在体内研究 SOD1 的生物学效应。应用 Western blot、ROS 测定和甘油三酯测定来研究 SOD1 在 NPC 中发挥促生存作用的潜在分子机制。
我们观察到 NPC 组织中 SOD1 的显著上调，高 SOD1 表达是预后不良的预测因子，并且与不良预后相关。我们在体外和体内都证实了 SOD1 的促生存作用。我们证明了 SOD1 的这些机制部分存在是为了维持低水平的超氧阴离子，并通过增强 CPT1A 介导的脂肪酸氧化来避免脂质滴的积累。
这项研究的结果表明，SOD1 是一种有潜力的预后生物标志物和 NPC 治疗的有前途的靶点。
