Rana Ezzeddini1, Mohammad Taghikhani2, Mohammad Hossein Somi3, Nasser Samadi4, Mohammad Javad Rasaee5. 1. Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran. 2. Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran. Electronic address: Taghi_mo@modares.ac.ir. 3. Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. 4. Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Biochemistry, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran. 5. Department of Medical Biotechnology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran. Electronic address: Rasaee_m@modares.ac.ir.
Abstract
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-1α on FASN and SREBP-1c regulation in GA. MAIN METHODS: AGS cell line was cultured in normoxic and hypoxic conditions, and HIF-1α, FASN and SREBP-1c gene expression were analyzed by qRT-PCR and Western blot. Serum HIF-1α, 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-1α were determined by qRT-PCR. KEY FINDINGS: In vitro findings indicate upregulation of HIF-1α, FASN and SREBP-1c gene and protein expression in the hypoxic culture of AGS cells. High circulating levels of HIF-1α and FASN were significantly observed in GA patients compared to the controls. HIF-1α, 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-1α and FASN and expression of HIF-1α, 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-1α and SREBP-1c are consistent with a possible up-regulation of FASN upon induction of HIF-1α through SREBP-1c.
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-1α on FASN and SREBP-1c regulation in GA. MAIN METHODS: AGS cell line was cultured in normoxic and hypoxic conditions, and HIF-1α, FASN and SREBP-1c gene expression were analyzed by qRT-PCR and Western blot. Serum HIF-1α, 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-1α were determined by qRT-PCR. KEY FINDINGS: In vitro findings indicate upregulation of HIF-1α, FASN and SREBP-1c gene and protein expression in the hypoxic culture of AGS cells. High circulating levels of HIF-1α and FASN were significantly observed in GA patients compared to the controls. HIF-1α, 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-1α and FASN and expression of HIF-1α, 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-1α and SREBP-1c are consistent with a possible up-regulation of FASN upon induction of HIF-1α through SREBP-1c.
Authors: Zhi Zheng; Yuxi Shang; Rui Xu; Xiaosheng Yan; Xi Wang; Jun Cai; Zhigang Bai; Xiaoye Liu; Jie Yin; Jun Zhang; Zhongtao Zhang Journal: Am J Cancer Res Date: 2022-06-15 Impact factor: 5.942
Authors: Zhaodong Ji; Yan Shen; Xu Feng; Yue Kong; Yang Shao; Jiao Meng; Xiaofei Zhang; Gong Yang Journal: Front Oncol Date: 2020-10-19 Impact factor: 6.244