Towards an Epigenetic Treatment of Leiomyomas?

Vaiman, Daniel

doi:10.1210/endocr/bqaa172

Cited by 4 publications

(3 citation statements)

References 5 publications

(4 reference statements)

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“…On the other hand, hypoxia can result in increased production of reactive oxygen species (ROS), which can affect ferrous ion availability for TET enzymatic activity [ 151 ]. In addition, under hypoxia, cellular concentrations of oncometabolites such as fumarate can affect TET activity [ 152 ].…”

Section: Role Of Tet Enzymes In Uf Developmentmentioning

confidence: 99%

“…Locus-specific genomic analyses revealed differential methylation of genes involved in cell differentiation/proliferation, such as at ESR1 , associated with altered mRNA levels, indicating a clear impact of 5′-Aza treatment in inducing genome demethylation. [ 50 , 152 ]. A mouse model of xenografts of human UF explants under the renal capsule was treated with 5′-Aza and showed a massive regression in the tumor size (36% of the size observed in the controls) [ 29 ].…”

Section: Demethylating Agents and Uf Developmentmentioning

confidence: 99%

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Epigenetic Regulation in Uterine Fibroids—The Role of Ten-Eleven Translocation Enzymes and Their Potential Therapeutic Application

Włodarczyk

Nowicka

Ciebiera

et al. 2022

IJMS

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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.

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Section: Role Of Tet Enzymes In Uf Developmentmentioning

confidence: 99%

Section: Demethylating Agents and Uf Developmentmentioning

confidence: 99%

Epigenetic Regulation in Uterine Fibroids—The Role of Ten-Eleven Translocation Enzymes and Their Potential Therapeutic Application

Włodarczyk

Nowicka

Ciebiera

et al. 2022

IJMS

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“…Together, these findings suggest that DNA methylation might play a key role in the pathogenesis of uterine leiomyoma by altering the normal myometrial mRNA expression profile. Further studies involving epigenetic modulators such as 5 -Aza-Cytidine could lead to novel treatments that slow tumor growth by depleting the stem cells through specific demethylation mechanisms [93,122].…”

Section: Epigeneticsmentioning

confidence: 99%

Molecular and Cellular Insights into the Development of Uterine Fibroids

Machado-Lopez

Simón

Mas

2021

IJMS

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Uterine leiomyomas represent the most common benign gynecologic tumor. These hormone-dependent smooth-muscle formations occur with an estimated prevalence of ~70% among women of reproductive age and cause symptoms including pain, abnormal uterine bleeding, infertility, and recurrent abortion. Despite the prevalence and public health impact of uterine leiomyomas, available treatments remain limited. Among the potential causes of leiomyomas, early hormonal exposure during periods of development may result in developmental reprogramming via epigenetic changes that persist in adulthood, leading to disease onset or progression. Recent developments in unbiased high-throughput sequencing technology enable powerful approaches to detect driver mutations, yielding new insights into the genomic instability of leiomyomas. Current data also suggest that each leiomyoma originates from the clonal expansion of a single transformed somatic stem cell of the myometrium. In this review, we propose an integrated cellular and molecular view of the origins of leiomyomas, as well as paradigm-shifting studies that will lead to better understanding and the future development of non-surgical treatments for these highly frequent tumors.

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