ArticleLeukemia research2016
Possible role of intragenic DNA hypermethylation in gene silencing of the tumor suppressor gene NR4A3 in acute myeloid leukemia.
Article in Leukemia research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 20 citations in OpenAlex.
- Investigation methylation status of tumor suppressor geneMolecular biology research communications · 2025Article
- NR4A3 inhibits the tumor progression of hepatocellular carcinoma by inducing cell cycle G0/G1 phase arrest and upregulation of CDKN2AIP expression.International journal of biological sciences · 2024Article
- Epigenetic modulations in cancer: predictive biomarkers and potential targets for overcoming the resistance to topoisomerase I inhibitors.Annals of medicine · 2023Review
- Functional association of NR4A3 downregulation with impaired differentiation in myeloid leukemogenesis.Annals of hematology · 2022Article
- GSK3B Overexpression Alleviates Posttraumatic Osteoarthritis in Mice by Promoting DNMT1-Mediated Hypermethylation of NR4A3 Promoter.Disease markers · 2022Article
- Role of NR4A family members in myeloid cells and leukemia.Current research in immunology · 2022Article
- Article
- Genome-wide methylation sequencing identifies progression-related epigenetic drivers in myelodysplastic syndromes.Cell death & disease · 2020Article
- miR-665 expression predicts poor survival and promotes tumor metastasis by targeting NR4A3 in breast cancer.Cell death & disease · 2019Article
- DNA methylation regulates TMEM16A/ANO1 expression through multiple CpG islands in head and neck squamous cell carcinoma.Scientific reports · 2017Article
Corrections and comments
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Authors and funding
22 authors at 3 institutions in 2 countries.
Funding
Abstract
Expression of the tumor suppressor gene NR4A3 is silenced in the blasts of acute myeloid leukemia (AML), irrespective of the karyotype. Although the transcriptional reactivation of NR4A3 is considered to have a broad-spectrum anti-leukemic effect, the therapeutic modalities targeting this gene have been hindered by our minimal understanding of the transcriptional mechanisms regulating its expression, particularly in human AML. Here we show the role of intragenic DNA hypermethylation in reducing the expression of NR4A3 in AML. Bisulfite sequencing analysis revealed that CpG sites at the intragenic region encompassing exon 3 of NR4A3, but not the promoter region, are hypermethylated in AML cell lines and primary AML cells. A DNA methyltransferase inhibitor restored the expression of NR4A3 following a reduction in DNA methylation levels at intragenic CpG sites. The in silico data revealed an enrichment of H3K4me1 and H2A.Z at exon 3 of NR4A3 in human non-malignant cells but that was excluded specifically in leukemia cells with CpG hypermethylation. This suggests that exon 3 represents a functional regulatory element involved in the transcriptional regulation of NR4A3. Our findings improve the current understanding of the mechanism underlying NR4A3 silencing and facilitate the development of NR4A3-targeted therapy.
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