A novel cuproptosis-related prognostic gene signature and validation of differential expression in hepatocellular carcinoma

Frontiers in Pharmacology, Journal Year: 2023, Volume and Issue: 13

Published: Jan. 10, 2023

Background: Cuproptosis is a newly discovered form of programmed cell death, which characterized by accumulation intra-cellular copper ion leading to the aggregation lipoproteins and destabilization Fe-S cluster proteins in mitochondrial metabolism, thereby affecting prognosis patients with cancer. However, role cuproptosis-related genes (CRGs) hepatocellular carcinoma (HCC) remains elusive. Methods: Mutation signature, copy number variation expression 10 CRGs were assessed HCC from TCGA-LIHC dataset. ICGC-LIRI-JP dataset was used as further validation cohort. The least absolute shrinkage selection operator (LASSO) construct prognostic model. Kaplan Meier curves, time-ROC nomogram, univariate multivariate Cox regression utilized evaluate predictive efficacy CRGs-score. Immune infiltration analyzed CIBERSOFT, ssGSEA algorithm, TIMER database. validated qPCR both in-vitro in-vivo. Drug sensitivity analysis performed pRRophetic. Results: All differentially expressed 5 out them (CDKN2A, DLAT, GLS, LIPT1, MTF1) correlated patient survival. These signature selected LASSO establish model stratify into high low CRGs-score subgroups. High associated worse prognosis. Subsequently, verified that an independent cancer risk factor clinical factors including stage grade. Nomogram integrating well predict revealed immune checkpoint significantly enhanced group, especially PD-1 PD-L1. An cohort (ICGC) confirmed stable universally applicable indicator predicting Concordantly, five also human lines mouse In addition, we targeted therapies between groups. Conclusion: This study elucidated dysregulated cohort, in-vivo models. might be applied novel HCC.

Language: Английский

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Glutamine metabolic reprogramming in hepatocellular carcinoma

Frontiers in Molecular Biosciences, Journal Year: 2023, Volume and Issue: 10

Published: Aug. 11, 2023

Hepatocellular carcinoma (HCC) is a lethal disease with limited management strategies and poor prognosis. Metabolism alternations have been frequently unveiled in HCC, including glutamine metabolic reprogramming. The components of metabolism, such as synthetase, glutamate dehydrogenase, glutaminase, metabolites, metabolite transporters, are validated to be potential biomarkers HCC. Increased consumption confirmed which fuels proliferation by elevated dehydrogenase or upstream signals. Glutamine metabolism also serves nitrogen source for amino acid nucleotide anabolism. In addition, more converts glutathione an antioxidant HCC protect cells from oxidative stress. Moreover, reprogramming activates the mTORC signaling pathway support tumor cell proliferation. targeting therapy includes deprivation, related enzyme inhibitors, transporters inhibitors. Together, plays pivotal role identification, proliferation, progression.

Language: Английский

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The retina and retinal pigment epithelium differ in nitrogen metabolism and are metabolically connected

Journal of Biological Chemistry, Journal Year: 2020, Volume and Issue: 295(8), P. 2324 - 2335

Published: Jan. 17, 2020

Defects in energy metabolism either the retina or immediately adjacent retinal pigment epithelium (RPE) underlie degeneration, but metabolic dependence between and RPE remains unclear. Nitrogen-containing metabolites such as amino acids are essential for metabolism. Here, we found that 15N-labeled ammonium is predominantly assimilated into glutamine both RPE/choroid ex vivo [15N]Ammonium tracing show that, like brain, can synthesize asparagine from ammonium, liver cannot. However, unless present at toxic concentrations, cannot be recycled glutamate RPE/choroid. Tracing with uses aspartate transaminase de novo synthesis of glutamate, glutamine, aspartate, whereas multiple transaminases to utilize acids. Retina consumes more leucine than RPE, little catabolized. The serine glycine active limited retina. not retina, alanine mitochondrial substrates through pyruvate carrier. when carrier inhibited, may directly enter mitochondria those RPE. In conclusion, our results demonstrate differ nitrogen highlight supports acid

Language: Английский

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Protective effect of metformin on BPA-induced liver toxicity in rats through upregulation of cystathionine β synthase and cystathionine γ lyase expression

The Science of The Total Environment, Journal Year: 2020, Volume and Issue: 750, P. 141685 - 141685

Published: Aug. 12, 2020

Language: Английский

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20,000 picometers under the OMM: diving into the vastness of mitochondrial metabolite transport

EMBO Reports, Journal Year: 2020, Volume and Issue: 21(5)

Published: April 23, 2020

Language: Английский

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