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

Abstract

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.Electronic supplementary materialThe online version of this article (10.1186/s12964-018-0240-3) contains supplementary material, which is available to authorized users.

SOD1 is essential for oncogene-driven mammary tumor formation but dispensable for normal development and proliferation

“…5m). These results are consistent with previous reports of the induction of apoptosis in established cancer cell lines following treatment with SOD1 inhibitors 2,3,40,44 .…”

Cross talk between SOD1 and the mitochondrial UPR in cancer and neurodegeneration

“…They further showed that increased hydrogen peroxide levels leads to p38 MAPK activation and subsequently results in a decrease in the anti-apoptotic factor MCL1 98 . It was also recently reported that SOD1 inhibition in nasopharyngeal carcinoma inhibits cell growth and promotes apoptosis 99 . These observations suggest that one mechanism by which SOD1 inhibition reduces cancer cell growth is through apoptosis.…”

Genetic polymorphisms of superoxide dismutase 1 are associated with the serum lipid profiles of Han Chinese adults in a sexually dimorphic manner

“…polymorphisms have contributions to the most nonfamilial dyslipidemia with complex molecular mechanisms. The previous animal studies demonstrated the antioxidant role of SOD1 to modulate the redox homeostasis in lipid metabolism [13][14][15], and cholesterol metabolism was affected by SOD1 even independent of its antioxidant activity via inhibiting the activity of 3-hydroxy-3-methylglutaryl CoA reductase and promoting the low-density lipoprotein receptor pathway in hepatocarcinoma cells [16]. SOD1 was also bound to almost all classes of circulating lipoproteins with relative high activity in low and high density lipoproteins [7], which partly underlay its potential in lipid metabolism.…”

“…Supraphysiological levels of ROS are extremely detrimental to DNA, lipids, proteins, and normal cellular metabolism [10,11], and have a strong potential to disturb the lipid metabolism [12]. The Sod1 knockout mice were characterized by lipid accumulation in liver and abnormal circulating lipid profiles [13,14], and the inhibition of SOD1 function in nasopharyngeal carcinoma connived the accumulation of lipid droplets [15]. SOD1 also affected cholesterol metabolism in human hepatocarcinoma cells [16] and its presence in human serum lipoproteins suggested its crucial role in the lipid transport [7].…”

“…Though the previous studies revealed that the knockout/inhibition of SOD1 induced disorders of lipid metabolism [3,[13][14][15][16] and the SNPs of SOD1 may correlate with some metabolic disorders [19-21, 25, 26, 31, 32], no epidemiologic studies were yet conducted to investigate the association of SOD1 SNPs and dyslipidemia, not to mention the effect of gender differences on the association. Therefore, the objective of this study was trying to understand the situation.…”