ArticleThe Journal of biological chemistry2014
The epigenetic drug 5-azacytidine interferes with cholesterol and lipid metabolism.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
22 citing papers in PubMed, 48 citations in OpenAlex.
- Cholesterol Reprogramming in Acute Myeloid Leukemia: Integrating Tumor-Intrinsic Metabolism and Immune Crosstalk.Diseases (Basel, Switzerland) · 2026Review
- Lead-induced Hepatotoxicity in Rat Hepatocytes: a Transcriptomic Network Analysis Reveals Key Molecular Insights.Biological trace element research · 2026Article
- DNMT3A in cancer: from epigenetic writer to oncogenic driver.Clinical epigenetics · 2026Review
- Is the combination of Myelodysplastic syndromes and pulmonary fibrosis accidental or inevitable?Multidisciplinary respiratory medicine · 2025Article
- DNA methylation and demethylation in adipocyte biology: roles of DNMT and TET proteins in metabolic disorders.Frontiers in endocrinology · 2025Review
- An Overview on Lipid Droplets Accumulation as Novel Target for Acute Myeloid Leukemia Therapy.Biomedicines · 2023Review
- Global Trends of Lipid Metabolism Research in Epigenetics Field: A Bibliometric Analysis from 2012-2021.International journal of environmental research and public health · 2023Article
- Titanium Dioxide Nanoparticles Altered the lncRNA Expression Profile in Human Lung Cells.International journal of environmental research and public health · 2023Article
- A survival prediction model and nomogram based on immune-related gene expression in chronic lymphocytic leukemia cells.Frontiers in medicine · 2022Article
- Article
- Long non-coding RNA levels can be modulated by 5-azacytidine in Schistosoma mansoni.Scientific reports · 2020Article
- Triciribine increases LDLR expression and LDL uptake through stabilization of LDLR mRNA.Scientific reports · 2018Article
- The anti-fecundity effect of 5-azacytidine (5-AzaC) on Schistosoma mansoni is linked to dis-regulated transcription, translation and stem cell activities.International journal for parasitology. Drugs and drug resistance · 2018Article
- Epigenetic modifications in hyperhomocysteinemia: potential role in diabetic retinopathy and age-related macular degeneration.Oncotarget · 2018Article
- Transcriptome profile analysis of leg muscle tissues between slow- and fast-growing chickens.PloS one · 2018Article
- A systematic assessment of chemical, genetic, and epigenetic factors influencing the activity of anticancer drug KP1019 (FFC14A).Oncotarget · 2017Article
- Slfn2 mutation-induced loss of T-cell quiescence leads to elevated de novo sterol synthesis.Immunology · 2017Article
- Article
- Trafficking Dynamics of PCSK9-Induced LDLR Degradation: Focus on Human PCSK9 Mutations and C-Terminal Domain.PloS one · 2016Article
- A clinical-molecular update on azanucleoside-based therapy for the treatment of hematologic cancers.Clinical epigenetics · 2016Review
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 2 countries.
Funding
Abstract
DNA methylation and histone acetylation inhibitors are widely used to study the role of epigenetic marks in the regulation of gene expression. In addition, several of these molecules are being tested in clinical trials or already in use in the clinic. Antimetabolites, such as the DNA-hypomethylating agent 5-azacytidine (5-AzaC), have been shown to lower malignant progression to acute myeloid leukemia and to prolong survival in patients with myelodysplastic syndromes. Here we examined the effects of DNA methylation inhibitors on the expression of lipid biosynthetic and uptake genes. Our data demonstrate that, independently of DNA methylation, 5-AzaC selectively and very potently reduces expression of key genes involved in cholesterol and lipid metabolism (e.g. PCSK9, HMGCR, and FASN) in all tested cell lines and in vivo in mouse liver. Treatment with 5-AzaC disturbed subcellular cholesterol homeostasis, thereby impeding activation of sterol regulatory element-binding proteins (key regulators of lipid metabolism). Through inhibition of UMP synthase, 5-AzaC also strongly induced expression of 1-acylglycerol-3-phosphate O-acyltransferase 9 (AGPAT9) and promoted triacylglycerol synthesis and cytosolic lipid droplet formation. Remarkably, complete reversal was obtained by the co-addition of either UMP or cytidine. Therefore, this study provides the first evidence that inhibition of the de novo pyrimidine synthesis by 5-AzaC disturbs cholesterol and lipid homeostasis, probably through the glycerolipid biosynthesis pathway, which may contribute mechanistically to its beneficial cytostatic properties.
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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.