Clinical importance of FASN in relation to HIF-1α and SREBP-1c in gastric adenocarcinoma
Clinical importance of FASN in relation to HIF-1α and SREBP-1c in gastric adenocarcinoma
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DOI：
10.1016/j.lfs.2019.03.056
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发表时间：
2019-05-01
期刊：
影响因子：
6.1
通讯作者：
Rasaee, Mohammad Javad
中科院分区：
文献类型：
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作者：
Ezzeddini, Rana;Taghikhani, Mohammad;Rasaee, Mohammad Javad
目的：识别沿着胃腺癌（GA）肿瘤发生途径的脂质代谢改变可能导致潜在的诊断，有效的预测和有前途的治疗策略的新方法。本研究旨在探讨HIF-1 α在GA中对FXR和SREBP-1c调控的可能作用。主要方法：在常氧和低氧条件下培养AGS细胞系，采用qRT-PCR和Western blot分析HIF-1 α、FXR和SREBP-1c基因表达。采用ELISA法检测112例GA患者和156例正常对照组血清中HIF-1 α、FXR和胰岛素浓度，免疫组化法检测SREBP-1c表达。通过qRT-PCR测定组织中SREBP-1c、FXR和HIF-1 α的mRNA表达。关键发现：体外研究结果表明，在缺氧培养的AGS细胞中，HIF-1 α、FXR和SREBP-1c基因和蛋白表达上调。与对照组相比，在GA患者中显著观察到高循环水平的HIF-1 α和FGF 1 α。与对照组相比，GA中的HIF-1 α、SREBP-1c和FGF基因表达更高。此外，与对照相比，GA组织中SREBP-1c蛋白水平增强。此外，升高的血清水平的HIF-1 α和FREBP和HIF-1 α，SREBP-1c和FREBP基因的表达与不利的临床病理特征，如弥漫型肿瘤和生存差。
Aims: Identifying alterations in lipid metabolism along gastric adenocarcinoma (GA) tumorigenesis pathways could lead to a new approach for potential diagnosis, efficient prediction and promising therapeutic strategies. This study aimed to identify the possible effect of HIF-1 alpha on FASN and SREBP-1c regulation in GA.Main methods: AGS cell line was cultured in normoxic and hypoxic conditions, and HIF-1 alpha, FASN and SREBP-1c gene expression were analyzed by qRT-PCR and Western blot. Serum HIF-1 alpha, FASN and insulin concentration were measured in 112 GA patients and 156 control cases by ELISA, and immunohistochemical method was employed to analyze SREBP-1c expression. Tissue mRNA expression of SREBP-1c, FASN and HIF-1 alpha were determined by qRT-PCR.Key findings: In vitro findings indicate upregulation of HIF-1 alpha, FASN and SREBP-1c gene and protein expression in the hypoxic culture of AGS cells. High circulating levels of HIF-1 alpha and FASN were significantly observed in GA patients compared to the controls. HIF-1 alpha, SREBP-1c and FASN gene expression were higher in GA vs. controls. In addition, SREBP-1c protein level was enhanced in GA tissues compared to controls. Furthermore, elevated serum levels of HIF-1a and FASN and expression of HIF-1 alpha, SREBP-1c and FASN genes were associated with unfavorable clinicopathological features such as diffuse type tumor and poor survival.Significance: The results by correlating increased levels of FASN to those of HIF-1 alpha and SREBP-1c are consistent with a possible up-regulation of FASN upon induction of HIF-1 alpha through SREBP-1c.