Metabolomics study of the metabolic changes in hepatoblastoma cells in response to NTCP/SLC10A1 overexpression. (August 2020)

• Record Type: Journal Article
• Authors: Wang, Jing; Tian, Ruicheng; Shan, Yuhua; Li, Jingjing; Gao, Hongxiang; Xie, Chenjie; Ma, Yimei; Wu, Yun; Ji, Bin; Gu, Song; Xu, Min
• Is Part Of: International journal of biochemistry & cell biology. Volume 125(2020)
• Publication Date: 2020-08
• Subjects: HB hepatoblastoma -- SLC10A1 solute carrier family 10 member -- NTCP Na+-taurocholate cotransporting polypeptide -- MS mass spectrometry -- NMR nuclear magnetic resonance -- SDS-PAGE sodium dodecyl sulfate-polyacrylamide gel electrophoresis -- PVDF polyvinylidene fluoride -- VIP variable importance in the projection -- ESI electrospray ionization -- RT retention time -- MZ mass-to-charge ratio -- MEM minimum essential medium -- FBS fetal bovine serum; Hepatoblastoma -- NTCP/SLC10A1 -- Metabonomics -- Purine metabolism -- Adenosine -- HIF1α; Biochemistry -- Periodicals; Cytology -- Periodicals; Biochemistry -- Periodicals; Cell Biology -- Periodicals; Biochimie -- Périodiques; Cytologie -- Périodiques; Biochimie; Cytologie; Biochemistry; Cytology; Ressource Internet (Descripteur de forme); Périodique électronique (Descripteur de forme); Periodicals; 572.05
• DOI: 10.1016/j.biocel.2020.105773
• Languages: English
• ISSNs: 1357-2725

Abstract

Abstract: NTCP (SLC10A1) has been well recognized as a basolateral (sinusoidal) Na+-bile acid co-transporter that mediates the hepatic uptake of bile acids. However, little is known about the effects of NTCP (SLC10A1) on hepatoblastoma (HB) and its underlying metabolic mechanisms. In this study, we found that NTCP (SLC10A1) expression was downregulated in HB cells and tissues, and it was demonstrated that NTCP (SLC10A1) reduced cell viability, promoted cell cycle arrest and induced apoptosis of HB cells. The metabolic profiles of HB cells with NTCP (SLC10A1) overexpression were further examined to determine their biochemical alterations and deepen our understanding on the metabolic regulation of NTCP (SLC10A1) overexpression. The metabolomics study based on ultra performance liquid chromatography-mass spectrometry revealed alterations in the metabolites of HB cells following NTCP (SLC10A1) overexpression. Next, we stably overexpressed NTCP (SLC10A1) in HepG2 cells, and found that NTCP (SLC10A1)-overexpressing cells could inhibit the production of adenosine and decreased both mRNA and protein levels of HIF1α. Further overexpression of HIF1α in the NTCP (SLC10A1)-overexpression group restored the production of adenosine. Collectively, these findings provide strong evidence that NTCP (SLC10A1) overexpression significantly disrupts the metabolism of adenosine in HB cells and highlight that NTCP (SLC10A1) mediates adenosine production mainly through HIF1α.