ArticleMolecular endocrinology (Baltimore, Md.)2013
Expression profiling of nuclear receptors identifies key roles of NR4A subfamily in uterine fibroids.
Article in Molecular endocrinology (Baltimore, Md.), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 31 citations in OpenAlex.
- UTERINE FIBROIDS.Physiological reviews · 2025Review
- Nuclear receptors in health and disease: signaling pathways, biological functions and pharmaceutical interventions.Signal transduction and targeted therapy · 2025Review
- Epigenomic and enhancer dysregulation in uterine leiomyomas.Human reproduction update · 2022Review
- Uterine Fibroids: Hiding in Plain Sight.Physiology (Bethesda, Md.) · 2022Review
- Epigenomic tensor predicts disease subtypes and reveals constrained tumor evolution.Cell reports · 2021Article
- Cross‑validation of genes potentially associated with neoadjuvant chemotherapy and platinum‑based chemoresistance in epithelial ovarian carcinoma.Oncology reports · 2020Article
- Function of Nr4a Orphan Nuclear Receptors in Proliferation, Apoptosis and Fuel Utilization Across Tissues.Cells · 2019Review
- Endometriosis and nuclear receptors.Human reproduction update · 2019Review
- Effect of HIFU on endometrial receptivity and sex hormone level in uterine fibroid patients and analysis of influencing factors for its treatment rate.Experimental and therapeutic medicine · 2019Article
- A Role for Progesterone-Regulated sFRP4 Expression in Uterine Leiomyomas.The Journal of clinical endocrinology and metabolism · 2017Article
- Adenovirus-mediated expression of orphan nuclear receptor NR4A2 targeting hepatic stellate cell attenuates liver fibrosis in rats.Scientific reports · 2016Article
- Role of vitamin D in uterine fibroid biology.Fertility and sterility · 2015Review
- Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Uterine fibroids (UFs), also known as uterine leiomyomas, are benign, fibrotic smooth muscle tumors. Although the GnRH analog leuprolide acetate that suppresses gonadal steroid hormones is used as a treatment, it has significant side effects, thereby limiting its use. Availability of more effective therapy is limited because of a lack of understanding of molecular underpinnings of the disease. Although ovarian steroid hormones estrogen and progesterone and their receptors are clearly involved, the role of other nuclear receptors (NRs) in UFs is not well defined. We used quantitative real-time PCR to systematically profile the expression of 48 NRs and identified several NRs that were aberrantly expressed in UFs. Among others, expression of NR4A subfamily members including NGFIB (NR4A1), NURR1 (NR4A2), and NOR1 (NR4A3) were dramatically suppressed in leiomyoma compared with the matched myometrium. Restoration of expression of each of these NR4A members in the primary leiomyoma smooth muscle cells decreased cell proliferation. Importantly, NR4As regulate expressions of the profibrotic factors including TGFβ3 and SMAD3, and several collagens that are key components of the extracellular matrix. Finally, we identify NR4A members as targets of leuprolide acetate treatment. Together, our results implicate several NRs including the NR4A subfamily in leiomyoma etiology and identify NR4As as potential therapeutic targets for treating fibrotic diseases.
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