ArticleThe American journal of pathology2011
DNA methylation suppresses expression of the urea cycle enzyme carbamoyl phosphate synthetase 1 (CPS1) in human hepatocellular carcinoma.
Article in The American journal of pathology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers, 2 of them syntheses that pooled it.
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Who cites it
78 citing papers in PubMed, 2 syntheses or guidelines pooled it, 125 citations in OpenAlex.
- Computational Identification of Novel Stage-Specific Biomarkers in Colorectal Cancer Progression.PloS one · 2016Pooled it
- Drug treatment of inborn errors of metabolism: a systematic review.Archives of disease in childhood · 2013Pooled it
- CPS1: a multipurpose mitochondrial enzyme, bile protein, acute liver injury biomarker, and cytokine.Gut · 2026Review
- Urea cycle dysregulation and arginine pathways in the pathogenesis of NAFLD and NASH (Review).International journal of molecular medicine · 2026Review
- Reprogramming of nitrogen metabolism in tumors: mechanisms and therapeutic implications.Amino acids · 2026Review
- Crosstalk BetweenCancers · 2026Review
- Ammonia metabolism and ammonia-induced cell death: role in cancer therapy.Cell communication and signaling : CCS · 2025Review
- Investigating Liquid-Liquid Phase Separation in Lung Adenocarcinoma to Improve Prognostic Accuracy and Treatment Efficacy.Journal of cellular and molecular medicine · 2025Article
- Review
- Urea cycle dysregulation: a new frontier in cancer metabolism and immune evasion.Cell communication and signaling : CCS · 2025Review
- Enterocyte-like differentiation defines metabolic gene signatures of CMS3 colorectal cancers and provides therapeutic vulnerability.Nature communications · 2025Article
- Machine learning and multi-omics data reveal driver gene-based molecular subtypes in hepatocellular carcinoma for precision treatment.PLoS computational biology · 2024Article
- Roles of NOLC1 in cancers and viral infection.Journal of cancer research and clinical oncology · 2023Review
- Underexpression of Carbamoyl Phosphate Synthetase I as Independent Unfavorable Prognostic Factor in Intrahepatic Cholangiocarcinoma: A Potential Theranostic Biomarker.Diagnostics (Basel, Switzerland) · 2023Article
- Epigenetic reactivation of tumor suppressor genes with CRISPRa technologies as precision therapy for hepatocellular carcinoma.Clinical epigenetics · 2023Article
- Metabolic Reprogramming of HCC: A New Microenvironment for Immune Responses.International journal of molecular sciences · 2023Review
- Metabolism as a New Avenue for Hepatocellular Carcinoma Therapy.International journal of molecular sciences · 2023Review
- A prognostic model based on DNA methylation-related gene expression for predicting overall survival in hepatocellular carcinoma.Frontiers in oncology · 2023Article
- Genetics of enzymatic dysfunctions in metabolic disorders and cancer.Frontiers in oncology · 2023Review
- Ornithine aminotransferase and carbamoyl phosphate synthetase 1 involved in ammonia metabolism serve as novel targets for early stages of gastric cancer.Journal of clinical laboratory analysis · 2022Article
18 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
Carbamoyl phosphate synthetase 1 (CPS1) is a liver-specific, intramitochondrial, rate-limiting enzyme in the urea cycle. A previous study showed that CPS1 is the antigen for hepatocyte paraffin 1 antibody, a commonly used antibody in surgical pathology practice; and CPS1 expression appears to be down-regulated in liver cancer tissue and cell lines. The aim of this study is to understand how the CPS1 gene is regulated in liver carcinogenesis. In this report, we show that human hepatocellular carcinoma (HCC) cells do not express CPS1, whereas cultured human primary hepatocytes express abundant levels. In addition, CPS1 was silenced or down-regulated in liver tumor tissues compared with the matched noncancerous tissues. The expression of CPS1 in HCC cells was restored with a demethylation agent, 5-azacytidine. We show that two CpG dinucleotides, located near the transcription start site, and a CpG-rich region in the first intron were hypermethylated in HCC cells. The hypermethylation of the two CpG dinucleotides was also detected in HCC tumor tissues compared with noncancerous tissues. Further molecular analysis with mutagenesis indicated that the two CpG dinucleotides play a role in promoter activity of the CPS1 gene. In conclusion, our study demonstrates that DNA methylation is a key mechanism of silencing CPS1 expression in human HCC cells, and CPS1 gene hypermethylation of the two CpG dinucleotides is a potential biomarker for HCC.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.