ArticleReproductive sciences (Thousand Oaks, Calif.)2016
Identification of Polycomb Group Protein EZH2-Mediated DNA Mismatch Repair Gene MSH2 in Human Uterine Fibroids.
Article in Reproductive sciences (Thousand Oaks, Calif.), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 17 citations in OpenAlex.
- Epigenetic Regulation of Uterine Smooth Muscle Tumors: Histone Modifications in Uterine Fibroids and Leiomyosarcoma.Biology · 2026Review
- Transcriptomic and functional analysis of fibroid extracellular vesicles.Clinical science (London, England : 1979) · 2026Article
- Nutrition and Uterine Fibroids: Clinical Impact and Emerging Therapeutic Perspectives.Journal of clinical medicine · 2025Review
- Review
- Developmental reprogramming of myometrial stem cells by endocrine disruptor linking to risk of uterine fibroids.Cellular and molecular life sciences : CMLS · 2023Article
- Epigenetic Modulation of Inflammatory Pathways in Myometrial Stem Cells and Risk of Uterine Fibroids.International journal of molecular sciences · 2023Article
- Oxidative Stress and Antioxidants in Uterine Fibroids: Pathophysiology and Clinical Implications.Antioxidants (Basel, Switzerland) · 2023Review
- A View on Uterine Leiomyoma Genesis through the Prism of Genetic, Epigenetic and Cellular Heterogeneity.International journal of molecular sciences · 2023Review
- Comprehensive Review of Uterine Fibroids: Developmental Origin, Pathogenesis, and Treatment.Endocrine reviews · 2022Review
- Article
- The histone methyltransferase EZH2 is required for normal uterine development and function in mice†.Biology of reproduction · 2019Article
- Benign metastasizing leiomyoma presenting with miliary pattern and fatal outcome: Case report with molecular analysis & review of the literature.Respiratory medicine case reports · 2019Article
- miR-137 is a tumor suppressor in endometrial cancer and is repressed by DNA hypermethylation.Laboratory investigation; a journal of technical methods and pathology · 2018Article
- Aberrant chromatin remodeling in gynecological cancer.Oncology letters · 2017Article
- The Role of MicroRNAs in Development of Endometrial Cancer: A Literature Review.Journal of reproduction & infertilityReview
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Uterine fibroids (UFs) are benign smooth muscle neoplasms affecting up to 70% of reproductive age women. Treatment of symptomatic UFs places a significant economic burden on the US health-care system. Several specific genetic abnormalities have been described as etiologic factors of UFs, suggesting that a low DNA damage repair capacity may be involved in the formation of UF. In this study, we used human fibroid and adjacent myometrial tissues, as well as an in vitro cell culture model, to evaluate the expression of MutS homolog 2 (MSH2), which encodes a protein belongs to the mismatch repair system. In addition, we deciphered the mechanism by which polycomb repressive complex 2 protein, EZH2, deregulates MSH2 in UFs. The RNA expression analysis demonstrated the deregulation of MSH2 expression in UF tissues in comparison to its adjacent myometrium. Notably, protein levels of MSH2 were upregulated in 90% of fibroid tissues (9 of 10) as compared to matched adjacent myometrial tissues. Human fibroid primary cells treated with 3-deazaneplanocin A (DZNep), chemical inhibitor of EZH2, exhibited a significant increase in MSH2 expression (P < .05). Overexpression of EZH2 using an adenoviral vector approach significantly downregulated the expression of MSH2 (P < .05). Chromatin immunoprecipitation assay demonstrated that enrichment of H3K27me3 in promoter regions of MSH2 was significantly decreased in DZNep-treated fibroid cells as compared to vehicle control. These data suggest that EZH2-H3K27me3 regulatory mechanism dynamically changes the expression levels of DNA mismatch repair gene MSH2, through epigenetic mark H3K27me3. MSH2 may be considered as a marker for early detection of UFs.
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