Epigenetic Regulation in Uterine Fibroids—The Role of Ten-Eleven Translocation Enzymes and Their Potential Therapeutic Application |
| |
Authors: | Marta Wł odarczyk,Graż yna Nowicka,Michał Ciebiera,Mohamed Ali,Qiwei Yang,Ayman Al-Hendy |
| |
Abstract: | Uterine fibroids (UFs) are monoclonal, benign tumors that contain abnormal smooth muscle cells and the accumulation of extracellular matrix (ECM). Although benign, UFs are a major source of gynecologic and reproductive dysfunction, ranging from menorrhagia and pelvic pain to infertility, recurrent miscarriage, and preterm labor. Many risk factors are involved in the pathogenesis of UFs via genetic and epigenetic mechanisms. The latter involving DNA methylation and demethylation reactions provide specific DNA methylation patterns that regulate gene expression. Active DNA demethylation reactions mediated by ten-eleven translocation proteins (TETs) and elevated levels of 5-hydroxymethylcytosine have been suggested to be involved in UF formation. This review paper summarizes the main findings regarding the function of TET enzymes and their activity dysregulation that may trigger the development of UFs. Understanding the role that epigenetics plays in the pathogenesis of UFs may possibly lead to a new type of pharmacological fertility-sparing treatment method. |
| |
Keywords: | uterine fibroids 5-hydroxymethylocytosine TET enzymes DNA demethylation DNA methylation epigenetic regulation non-hormonal therapy |
|
|