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

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. Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.

Citation

Jing Wang, Ruicheng Tian, Yuhua Shan, Jingjing Li, Hongxiang Gao, Chenjie Xie, Yimei Ma, Yun Wu, Bin Ji, Song Gu, Min Xu. Metabolomics study of the metabolic changes in hepatoblastoma cells in response to NTCP/SLC10A1 overexpression. The international journal of biochemistry & cell biology. 2020 Aug;125:105773

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PMID: 32450267

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