Disrupting SOD1 activity inhibits cell growth and enhances lipid accumulation in nasopharyngeal carcinoma.

Disrupting SOD1 activity inhibits cell growth and enhances lipid accumulation in nasopharyngeal carcinoma.
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破坏 SOD1 活性可抑制鼻咽癌细胞生长并增强脂质积累

DOI:
10.1186/s12964-018-0240-3
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发表时间:
2018-06-11
期刊:
Cell communication and signaling : CCS
影响因子:
--
通讯作者:
Gong Q
Gong Q
中科院分区:
其他
文献类型:
--
作者:
Li S;Fu L;Tian T;Deng L;Li H;Xia W;Gong Q

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背景SOD 1是一种丰富的酶,已被研究作为抗氧化防御系统的调节剂,并且该酶被熟知为催化超氧化物歧化为过氧化氢。方法采用Western blot和免疫组化(IHC)方法检测鼻咽癌组织中SOD 1蛋白的表达。分别采用qRT-PCR和SOD活性试剂盒检测mRNA水平和SOD 1活性。采用Kaplan-Meier生存分析探讨SOD 1表达与鼻咽癌预后的关系。通过CCK-8、克隆形成和细胞凋亡测定在体外和通过异种移植小鼠模型在体内研究SOD 1的生物学效应。Western blotting、ROS检测和甘油三酯测定等方法探讨SOD 1在鼻咽癌组织中促生存作用的分子机制。结果SOD 1在鼻咽癌组织中表达显著上调,高表达是预后不良的预测因子,与预后不良相关。我们证实了SOD 1在体外和体内的促生存作用。我们证明,这些机制的SOD 1部分存在,以保持低水平的超氧阴离子,并避免通过增强CPT 1A介导的脂肪酸oxidation.ConclusionsThe结果的脂滴的积累这项研究表明,SOD 1是一个潜在的预后生物标志物和一个有前途的鼻咽癌治疗的目标。
BackgroundSOD1 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.MethodsIn 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.ResultsWe 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.ConclusionsThe results of this study indicate that SOD1 is a potential prognostic biomarker and a promising target for NPC therapy.
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