ArticleGenes & cancer2011
Epigenetic silencing of erythropoietin in human cancers.
Article in Genes & cancer, 2011. 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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Who cites it
22 citing papers in PubMed, 36 citations in OpenAlex.
- Epigenetic dichotomy in florid vs. gliotic proliferative diabetic retinopathy: hypomethylation of EGLN1 and MMP9 drives divergent pathogenic pathways in angiogenesis and fibrosis.Frontiers in endocrinology · 2026Article
- Catching cancer signals in the blood: Innovative pathways for early esophageal cancer diagnosis.World journal of gastroenterology · 2025Article
- Plasma DNA methylation detection for early screening, diagnosis, and monitoring of esophageal adenocarcinoma and squamous cell carcinoma.World journal of gastroenterology · 2024Article
- Ketone monoester ingestion increases postexercise serum erythropoietin concentrations in healthy men.American journal of physiology. Endocrinology and metabolism · 2023Article
- Differential Placental DNA Methylation ofFrontiers in pediatrics · 2022Article
- Exposomes to Exosomes: Exosomes as Tools to Study Epigenetic Adaptive Mechanisms in High-Altitude Humans.International journal of environmental research and public health · 2021Review
- Characterization of in vitro models of SLC30A10 deficiency.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2021Article
- Article
- DNA Methylation ofFrontiers in pediatrics · 2021Article
- RASSF10 is frequently epigenetically inactivated in kidney cancer and its knockout promotes neoplasia in cancer prone mice.Oncogene · 2020Article
- Epigenetic therapy of novel tumour suppressor ZAR1 and its cancer biomarker function.Clinical epigenetics · 2019Article
- Differential placental DNA methylation of VEGFA and LEP in small-for-gestational age fetuses with an abnormal cerebroplacental ratio.PloS one · 2019Article
- The tumor suppressor RASSF1A induces the YAP1 target geneOncotarget · 2017Article
- Renal Anemia Model Mouse Established by Transgenic Rescue with an Erythropoietin Gene Lacking Kidney-Specific Regulatory Elements.Molecular and cellular biology · 2017Article
- DNA methyltransferase inhibition restores erythropoietin production in fibrotic murine kidneys.The Journal of clinical investigation · 2016Article
- Quantitative profiling of chromatome dynamics reveals a novel role for HP1BP3 in hypoxia-induced oncogenesis.Molecular & cellular proteomics : MCP · 2014Article
- Systems biology approach to stage-wise characterization of epigenetic genes in lung adenocarcinoma.BMC systems biology · 2013Article
- Plasticity of renal erythropoietin-producing cells governs fibrosis.Journal of the American Society of Nephrology : JASN · 2013Article
- DNA methylation of distal regulatory sites characterizes dysregulation of cancer genes.Genome biology · 2013Article
- Characterization of the erythropoietin/erythropoietin receptor axis in a rat model of liver damage and cholangiocarcinoma development.Histochemistry and cell biology · 2013Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The glycoprotein hormone erythropoietin (EPO) is a key regulator in the production of red blood cells. EPO is produced mainly in the embryonic liver and kidney of adults. Other organs are also known to express varying amounts of EPO. In our study, we have analyzed the epigenetic regulation of EPO in human cancer cell lines by DNA methylation assays, chromatin immunoprecipitation, RT-PCR, and promoter analysis under different growth conditions. Moreover, the growth-related effects of ectopic EPO expression were analyzed in a head and neck cancer cell line. We found frequent DNA hypermethylation of the CpG island promoter and enhancer of EPO in different cancer cell lines. Aberrant methylation of EPO promoter was observed in primary lung, head and neck, breast, and liver cancers. Hypermethylation of EPO was associated with a decreased expression of EPO in cancer cells. Treatment of cancer cell lines with 5-aza-2'-deoxycytidine (Aza), an inhibitor of DNA methylation, reactivated EPO expression under hypoxia. In contrast, in the liver cancer cell line HepB3, the EPO promoter was unmethylated, and a high EPO expression was observed independently of Aza treatment. Moreover, in vitro hypermethylation of the EPO promoter and enhancer reduced expression of a reporter gene under normoxia and hypoxia. Induction of EPO under hypoxia was accompanied by increased histone H3 acetylation and reduced histone H3 lysine 9 trimethylation. In a head and neck cancer cell line, which exhibited low EPO levels, ectopic expression of EPO significantly enhanced proliferation under normoxia and hypoxia. In summary, we show that hypermethylation of regulatory sequences of EPO is frequently observed in tumors and that this aberrant methylation induces epigenetic silencing of EPO in cancer cells.
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