[NDRG2通过调节磷脂和甘油三酯代谢抑制肝细胞癌的肿瘤发生：代谢组学分析]
[NDRG2 inhibits tumorigenesis of hepatocellular carcinoma by regulating metabolism of phospholipids and triglyceride: a metabonomic analysis].
作者信息
Wang J, Yuan Y, Zhang K, Sun X, Bu X, Dong J, Wu Y, Tian H, Shen L
机构信息
Department of Pathogenic Biology, Medical College, Yan'an University, Yan'an 716000, China.
State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Air Force Military Medical University, Xi'an 710032, China.
出版信息
Nan Fang Yi Ke Da Xue Xue Bao. 2022 Dec 20;42(12):1765-1773. doi: 10.12122/j.issn.1673-4254.2022.12.03.
OBJECTIVE
To explore the role of the tumor suppressor gene 2 in regulating lipid metabolism in hepatoma cells.
METHODS
We analyzed the differential expression of gene between hepatocellular carcinoma tissues (=809) and normal liver tissues (=379) based on data from TNMplot database, and investigated the correlation between mRNA expression and the overall survival of the patients with hepatocellular carcinoma using THPA database, which was also used for analysis of expression levels in tumor cell lines for screening hepatoma cell lines. Human hepatoma cell line HepG2 was infected with a lentivirus containing cDNA, and the expression level of in the infected cells was detected using qPCR and Western blotting. Lipid metabolomics analysis was performed to analyze the regulatory effect of overexpression on lipid metabolism in HepG2 cells, and ELISA and Oil Red O staining were used to examine the changes in contents of phospholipids and triglyceride in -overexpressing HepG2 cells.
RESULTS
Analysis of the TNMplot database showed that expression level was significantly lower in hepatocellular carcinoma tissues than in normal liver tissues ( < 0.001). Analysis of THPA database showed that the patients with high mRNA levels had a longer survival time than those with low mRNA levels, and expression level was the highest in HepG2 cell line among the tumor cell lines. Metabolomics analysis showed that in HepG2 cells, overexpression led to changes in the contents of phospholipids, and among them lecithin PC, phosphatidyl glycerol PG, phosphatidyl ethanolamine PE, sphinophosphatidyl serine SM, and ceramide Cer exhibited significant changes. The results of ELISA and Oil Red O staining demonstrated that overexpression obviously reduced the contents of multiple phospholipids and significantly lowered the contents of triglyceride in HepG2 cells.
CONCLUSION
regulates tumorigenesis of hepatocellular carcinoma by modulating the metabolism of phospholipids and triglyceride.
目的
探讨肿瘤抑制基因2在调节肝癌细胞脂质代谢中的作用。
方法
基于TNMplot数据库的数据，分析809例肝细胞癌组织和379例正常肝组织中该基因的差异表达，并利用THPA数据库研究该基因mRNA表达与肝细胞癌患者总生存期的相关性，该数据库也用于分析肿瘤细胞系中的表达水平以筛选肝癌细胞系。用含该基因cDNA的慢病毒感染人肝癌细胞系HepG2，采用qPCR和蛋白质免疫印迹法检测感染细胞中该基因的表达水平。进行脂质代谢组学分析以分析该基因过表达对HepG2细胞脂质代谢的调节作用，采用酶联免疫吸附测定法（ELISA）和油红O染色检测该基因过表达的HepG2细胞中磷脂和甘油三酯含量的变化。
结果
TNMplot数据库分析显示，肝细胞癌组织中该基因的表达水平显著低于正常肝组织（P<0.001）。THPA数据库分析显示，该基因mRNA水平高的患者比该基因mRNA水平低的患者生存时间更长，且在肿瘤细胞系中HepG2细胞系中该基因的表达水平最高。代谢组学分析表明，在HepG2细胞中，该基因过表达导致磷脂含量发生变化，其中卵磷脂PC、磷脂酰甘油PG、磷脂酰乙醇胺PE、鞘磷脂酰丝氨酸SM和神经酰胺Cer表现出显著变化。ELISA和油红O染色结果表明，该基因过表达明显降低了HepG2细胞中多种磷脂的含量，并显著降低了甘油三酯的含量。
结论
该基因通过调节磷脂和甘油三酯的代谢来调控肝细胞癌的发生。
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