ArticleThe Journal of clinical endocrinology and metabolism2014
5-Hydroxymethylcytosine promotes proliferation of human uterine leiomyoma: a biological link to a new epigenetic modification in benign tumors.
Article in The Journal of clinical endocrinology and metabolism, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 51 citations in OpenAlex.
- Nutrition and Uterine Fibroids: Clinical Impact and Emerging Therapeutic Perspectives.Journal of clinical medicine · 2025Review
- UTERINE FIBROIDS.Physiological reviews · 2025Review
- Association of tet methylcytosine dioxygenase 2 and 5-hydroxymethylcytosine in endometrioid adenocarcinoma and its clinical significance.BMC women's health · 2024Article
- Epigallocatechin Gallate for the Treatment of Benign and Malignant Gynecological Diseases-Focus on Epigenetic Mechanisms.Nutrients · 2024Review
- Racial disparities between measures of area deprivation and financial toxicity, and uterine volume in myomectomy patients.BMC women's health · 2023Article
- Update on the Role and Regulatory Mechanism of Extracellular Matrix in the Pathogenesis of Uterine Fibroids.International journal of molecular sciences · 2023Review
- A View on Uterine Leiomyoma Genesis through the Prism of Genetic, Epigenetic and Cellular Heterogeneity.International journal of molecular sciences · 2023Review
- Epigenetic Features in Uterine Leiomyosarcoma and Endometrial Stromal Sarcomas: An Overview of the Literature.Biomedicines · 2022Review
- Comprehensive Review of Uterine Fibroids: Developmental Origin, Pathogenesis, and Treatment.Endocrine reviews · 2022Review
- Epigenomic and enhancer dysregulation in uterine leiomyomas.Human reproduction update · 2022Review
- Report of Exosomes Isolated from a Human Uterine Leiomyoma Cell Line and Their Impact on Endometrial Vascular Endothelial Cells.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Epigenetic Regulation in Uterine Fibroids-The Role of Ten-Eleven Translocation Enzymes and Their Potential Therapeutic Application.International journal of molecular sciences · 2022Review
- Analysis of Competitive Endogenous Mechanism and Survival Prognosis of Serum Exosomes in Ovarian Cancer Patients Based on Sequencing Technology and Bioinformatics.Frontiers in genetics · 2022Article
- Environmental Epigenetics and Genome Flexibility: Focus on 5-Hydroxymethylcytosine.International journal of molecular sciences · 2020Review
- Altered chromatin landscape and enhancer engagement underlie transcriptional dysregulation in MED12 mutant uterine leiomyomas.Nature communications · 2020Article
- Characterization of global 5-hydroxymethylcytosine in pediatric posterior fossa ependymoma.Clinical epigenetics · 2020Article
- Changes in DNA 5-Hydroxymethylcytosine Levels and the Underlying Mechanism in Non-functioning Pituitary Adenomas.Frontiers in endocrinology · 2020Article
- Pathogenomics of Uterine Fibroids Development.International journal of molecular sciences · 2019Review
- Article
- MicroRNA-21 promotes cell proliferation by targeting tumor suppressor TET1 in colorectal cancer.International journal of clinical and experimental pathology · 2018Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
contextUterine leiomyoma, or fibroids, represent the most common benign tumors of the female reproductive tract. A newly discovered epigenetic modification, 5-hydroxymethylation (5-hmC), and its regulators, the TET (Ten Eleven Translocation) enzymes, were implicated in the pathology of malignant tumors; however, their roles in benign tumors, including uterine fibroids, remain unknown.
objectiveTo determine the role of 5-hmC and TET proteins in the pathogenesis of leiomyoma using human uterine leiomyoma and normal matched myometrial tissues and primary cells.
design5-hmC levels were determined by ELISA and immunofluorescent staining in matched myometrial and leiomyoma tissues. TET expression was analyzed by quantitative RT-PCR and immunoblotting. TET1 or TET3 were silenced or inhibited by small interfering RNA or 2-hydroxyglutarate to study their effects on 5-hmC content and cell proliferation.
resultsWe demonstrated significantly higher 5-hmC levels in the genomic DNA of leiomyoma tissue compared to normal myometrial tissue. The increase in 5-hmC levels was associated with the up-regulation of TET1 or TET3 mRNA and protein expression in leiomyoma tissue. TET1 or TET3 knockdown significantly reduced 5-hmC levels in leiomyoma cells and decreased cell proliferation. Treatment with 2-hydroxyglutarate, a competitive TET enzyme inhibitor, significantly decreased both 5-hmC content and cell proliferation of leiomyoma cells.
conclusionAn epigenetic imbalance in the 5-hmC content of leiomyoma tissue, caused by up-regulation of the TET1 and TET3 enzymes, might lead to discovery of new therapeutic targets in leiomyoma.
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