The Mechanism and Function of Epigenetics in Uterine Leiomyoma Development

Qiwei Yang, Aymara Mas, Michael Peter Diamond, Ayman Al-Hendy

Research output: Contribution to journalReview article

43 Citations (Scopus)

Abstract

Uterine leiomyomas, also known as uterine fibroids, are the most common pelvic tumors, occurring in nearly 70% of all reproductive-aged women and are the leading indication for hysterectomy worldwide. The development of uterine leiomyomas involve a complex and heterogeneous constellation of hormones, growth factors, stem cells, genetic, and epigenetic abnormalities. An increasing body of evidence emphasizes the important contribution of epigenetics in the pathogenesis of leiomyomas. Genome-wide methylation analysis demonstrates that a subset of estrogen receptor (ER) response genes exhibit abnormal hypermethylation levels that are inversely correlated with their RNA expression. Several tumor suppressor genes, including Kruppel-like factor 11 (KLF11), deleted in lung and esophageal cancer 1 (DLEC1), keratin 19 (KRT19), and death-associated protein kinase 1 (DAPK1) also display higher hypermethylation levels in leiomyomas when compared to adjacent normal tissues. The important role of active DNA demethylation was recently identified with regard to the ten-eleven translocation protein 1 and ten-eleven translocation protein 3-mediated elevated levels of 5-hydroxymethylcytosine in leiomyoma. In addition, both histone deacetylase and histone methyltransferase are reported to be involved in the biology of leiomyomas. A number of deregulated microRNAs have been identified in leiomyomas, leading to an altered expression of their targets. More recently, the existence of side population (SP) cells with characteristics of tumor-initiating cells have been characterized in leiomyomas. These SP cells exhibit a tumorigenic capacity in immunodeficient mice when exposed to 17β-estradiol and progesterone, giving rise to fibroid-like tissue in vivo. These new findings will likely enhance our understanding of the crucial role epigenetics plays in the pathogenesis of uterine leiomyomas as well as point the way to novel therapeutic options.

Original languageEnglish (US)
Pages (from-to)163-175
Number of pages13
JournalReproductive Sciences
Volume23
Issue number2
DOIs
StatePublished - Feb 1 2016

Fingerprint

Leiomyoma
Epigenomics
Side-Population Cells
Protein Transport
Death-Associated Protein Kinases
Kruppel-Like Transcription Factors
Keratin-19
Histone Deacetylases
Neoplastic Stem Cells
Esophageal Neoplasms
Tumor Suppressor Genes
Hysterectomy
MicroRNAs
Estrogen Receptors
Methylation
Progesterone
Estradiol
Lung Neoplasms
Intercellular Signaling Peptides and Proteins
Stem Cells

Keywords

  • DNA methylation
  • TET proteins
  • epigenetics
  • histone modification
  • leiomyoma
  • miRNA
  • oxidative DNA demethylation
  • stem cells

ASJC Scopus subject areas

  • Obstetrics and Gynecology

Cite this

The Mechanism and Function of Epigenetics in Uterine Leiomyoma Development. / Yang, Qiwei; Mas, Aymara; Diamond, Michael Peter; Al-Hendy, Ayman.

In: Reproductive Sciences, Vol. 23, No. 2, 01.02.2016, p. 163-175.

Research output: Contribution to journalReview article

Yang, Qiwei ; Mas, Aymara ; Diamond, Michael Peter ; Al-Hendy, Ayman. / The Mechanism and Function of Epigenetics in Uterine Leiomyoma Development. In: Reproductive Sciences. 2016 ; Vol. 23, No. 2. pp. 163-175.
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