Multi-omics analyses reveal metabolic alterations regulated by hepatitis B virus core protein in hepatocellular carcinoma cells

Xie, Qiang; Fan, Fengxu; Wei, Wei; Yang, Liu; Xu, Zhongwei; Zhai, Linhui; Qi, Yingzi; Ye, Bingyu; Zhang, Yao; Basu, Sumit; Zhao, Zhihu; Wu, Junzhu; Xu, Ping

doi:10.1038/srep41089

Cited by 43 publications

(57 citation statements)

References 52 publications

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“…Furthermore, autocrine expression of TGF-β is responsible for differences in the stem and migratory phenotype of HCC cells 13 , 14 . Although several clues suggest that metabolic reprogramming may be a transcriptional hallmark in the process to liver carcinogenesis 6 – 8 , 15 , there is still no explanation for the heterogeneity of metabolic profiles found among the different HCC phenotypes, nor the metabolic adaptations of HCC cells to support their migration and invasion.…”

Section: Discussionmentioning

confidence: 99%

Role of the Transforming Growth Factor-β in regulating hepatocellular carcinoma oxidative metabolism

Soukupová

Malfettone

Hyroššová

et al. 2017

Sci Rep

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Transforming Growth Factor beta (TGF-β) induces tumor cell migration and invasion. However, its role in inducing metabolic reprogramming is poorly understood. Here we analyzed the metabolic profile of hepatocellular carcinoma (HCC) cells that show differences in TGF-β expression. Oxygen consumption rate (OCR), extracellular acidification rate (ECAR), metabolomics and transcriptomics were performed. Results indicated that the switch from an epithelial to a mesenchymal/migratory phenotype in HCC cells is characterized by reduced mitochondrial respiration, without significant differences in glycolytic activity. Concomitantly, enhanced glutamine anaplerosis and biosynthetic use of TCA metabolites were proved through analysis of metabolite levels, as well as metabolic fluxes from U-13C6-Glucose and U-13C5-Glutamine. This correlated with increase in glutaminase 1 (GLS1) expression, whose inhibition reduced cell migration. Experiments where TGF-β function was activated with extracellular TGF-β1 or inhibited through TGF-β receptor I silencing showed that TGF-β induces a switch from oxidative metabolism, coincident with a decrease in OCR and the upregulation of glutamine transporter Solute Carrier Family 7 Member 5 (SLC7A5) and GLS1. TGF-β also regulated the expression of key genes involved in the flux of glycolytic intermediates and fatty acid metabolism. Together, these results indicate that autocrine activation of the TGF-β pathway regulates oxidative metabolism in HCC cells.

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Section: Discussionmentioning

confidence: 99%

Role of the Transforming Growth Factor-β in regulating hepatocellular carcinoma oxidative metabolism

Soukupová

Malfettone

Hyroššová

et al. 2017

Sci Rep

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“…Previous study indicated that glycolysis and amino acid metabolism had a closely association with the development and progression of HCC by multi-omics analyses [28,29]. Moreover, abnormal lipid metabolism has also been found in HCC patients [30].…”

Section: Discussionmentioning

confidence: 99%

Identification of Prognostic Genes Associated with Expression Differentiation During Metabolism Process in Hepatocellular Carcinoma (HCC)

Yang¹,

Cao²,

Dou³

et al. 2020

Preprint

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Background: Metabolic disorders have attracted more and more attention from scientists in the research of various tumors, especially in hepatocellular carcinoma (HCC). The purpose of this study is to assess the prognostic significance of metabolism in HCC.Methods: The expression profile of metabolism-related gene (MRGs) were extracted from the cancer genome atlas (TCGA) database of 349 HCC-surviving patients. Subsequently, A series of biomedical computational algorithms were used to identify seven-MRGs signature as a prognostic model. GSEA analysis indicated the function and pathway enrichment of these MRGs. Then, drug sensitivity analysis found the hub gene, which tested by IHC staining.Results: 420 differential MRGs and 116 differential transcription factor (TFs) expression were extracted from HCC patients based on TCGA database. Metabolic disturbance might be involved in the development of HCC by GO and KEGG enrichment analyses. LASSO regression analysis constructed seven-MRGs signature (DHDH, ENO1, G6PD, LPCAT1, PDE6D, PIGU and PPAT), which were used to predict the prognosis of HCC patients. Further GSEA analysis found the function and pathway enrichment of these seven MRGs. Then, drug sensitivity analysis indicated G6PD might play a key role in the prognosis of HCC by chemoresistance. Finally, we used IHC staining to demonstrate the relationship of G6PD expression and clinical parameter in HCC patients.Conclusion: This study provides a potential clue for predicting the prognosis of HCC patients and further studies on HCC metabolism.

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“…Proteomics and metabolomics studies indicate that HBV core protein (HBc) significantly induces glycolysis in HCC cells. It may recruit Max-like protein X (MLX), a transcription factor, and facilitate its translocation to the nucleus, where it promotes the expression of glycolytic enzymes, such as aldolase C (ALDOC) and phosphoenolpyruvate carboxykinase (PCK1) 68 .…”

Section: Modulation Of Glucose Metabolic Signalingmentioning

confidence: 99%

Oncogenic virus-induced aerobic glycolysis and tumorigenesis

Chen

Wang

et al. 2018

J. Cancer

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Enhanced glycolysis under normoxic conditions is known as aerobic glycolysis or the Warburg effect and is a hallmark of many tumors. Viral infection may also induce aerobic glycolysis as it is required for replication and survival. Tumor viruses inducing aerobic glycolysis and lactate production during latent infection suggest a potential role of virus-induced glycolysis in tumorigenesis. Virus or virus-encoded proteins regulate glucose uptake and lactate export, increase the activity of glycolytic enzymes, and modulate glucose metabolic signals. Accumulating evidence suggests that virus-induced glycolysis may facilitate cell growth, transformation, migration, and invasion, but its significance in tumorigenesis remains unclear. We summarize the effects of oncogenic viruses on the metabolic shift to aerobic glycolysis and discuss the possible association of this metabolic reprogramming with tumor development and progression.

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Multi-omics analyses reveal metabolic alterations regulated by hepatitis B virus core protein in hepatocellular carcinoma cells

Cited by 43 publications

References 52 publications

Role of the Transforming Growth Factor-β in regulating hepatocellular carcinoma oxidative metabolism

Role of the Transforming Growth Factor-β in regulating hepatocellular carcinoma oxidative metabolism

Identification of Prognostic Genes Associated with Expression Differentiation During Metabolism Process in Hepatocellular Carcinoma (HCC)

Oncogenic virus-induced aerobic glycolysis and tumorigenesis

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