Differential expression of microRNA species in human uterine leiomyoma versus normal myometrium

Marsh, Erica E.; Lin, Zhihong; Yin, Ping; Milad, Magdy P.; Chakravarti, Debabrata; Bulun, Serdar E.

doi:10.1016/j.fertnstert.2007.05.074

Cited by 118 publications

(108 citation statements)

References 27 publications

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“…In cultured human uterine cell lines, we also showed that the high level of endogenous RECK protein was downregulated by miR-21 in HeLa cells, whereas the low level of endogenous RECK protein was up-regulated by the miR-21 inhibitor in Ishikawa cells. These data showed that RECK was not only the target gene of miR-21, but the endogenous RECK protein level was also regulated by miR- 21.…”

Section: Confirmation and Comparison Of Mirna Microarray Data-mentioning

confidence: 83%

MicroRNA Expression and Regulation in Mouse Uterus during Embryo Implantation

Ren

Liu

et al. 2008

Journal of Biological Chemistry

193

184

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MicroRNAs (miRNAs) are 21-24-nucleotide non-coding RNAs found in diverse organisms. Although hundreds of miRNAs have been cloned or predicted, only very few miRNAs have been functionally characterized. Embryo implantation is a crucial step in mammalian reproduction. Many genes have been shown to be significantly changed in mouse uterus during embryo implantation. However, miRNA expression profiles in the mouse uterus between implantation sites and inter-implantation sites are still unknown. In this study, miRNA microarray was used to examine differential expression of miRNAs in the mouse uterus between implantation sites and inter-implantation sites. Compared with inter-implantation sites, there were 8 up-regulated miRNAs at implantation sites, which were confirmed by both Northern blot and in situ hybridization. miR-21 was highly expressed in the subluminal stromal cells at implantation sites on day 5 of pregnancy. Because miR-21 was not detected in mouse uterus during pseudopregnancy and under delayed implantation, miR-21 expression at implantation sites was regulated by active blastocysts. Furthermore, we showed that Reck was the target gene of miR-21. Our data suggest that miR-21 may play a key role during embryo implantation.

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Section: Confirmation and Comparison Of Mirna Microarray Data-mentioning

confidence: 83%

MicroRNA Expression and Regulation in Mouse Uterus during Embryo Implantation

Ren

Liu

et al. 2008

Journal of Biological Chemistry

193

184

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“…A number of studies have been conducted to perform profiling and function analyses of miRNAs in human uterine leiomyoma using microarray and deep sequencing. 82,[127][128][129] These studies demonstrate that many miRNAs regulating cellular processes including cell proliferation, apoptosis, cell adhesion, WNT signaling, mitogen-activated protein kinase (MAPK) signaling, nuclear factor kB (NF-kB) activation, and insulin signaling are deregulated in leiomyoma when compared to normal tissues. Importantly, the predicted targets of these deregulated miRNAs including let-7, miR-21, miR-23b, miR-29b, and miR-197 in leiomyoma play an important role in the pathogenesis of leiomyoma.…”

Section: Dysregulation Of Mirna In Uterine Leiomyomamentioning

confidence: 99%

The Mechanism and Function of Epigenetics in Uterine Leiomyoma Development

et al. 2016

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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 teneleven 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 17b-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.

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“…Follow-up studies demonstrate abnormal global genomic methylation in UL compared to normal myometrium [Yamagata et al 2009], implicating possible epigenetic contributions to genetic susceptibility of UL development. Several miRNAs such as let7, miR-21, miR-93, miR-106b, and miR-200 are significantly deregulated in UL cells compared to normal myometrium [Marsh et al 2008]. Growing evidence indicates that steroid hormones E2 and P are the most important epigenetic regulators of growth factors, cytokines, chemokines, and extracellular matrix components that are so important for UL progression.…”

Section: Epigenetic Regulation Of Ulmentioning

confidence: 99%

Comparative systems genetics view of endometriosis and uterine leiomyoma: Two sides of the same coin?

Baranov

Ivaschenko

Yarmolinskaya

2016

Systems Biology in Reproductive Medicine

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Endometriosis (EM) and uterine leiomyoma (UL) are two most frequent benign tumors of monoclonal origin affecting about 30% of all women in their reproductive age. Modern molecular technologies have made a tremendous impact in understanding both disorders. Here is the first comparative analysis of molecular mechanisms underlying development of EM and UL as it looks from the platform of systems genetics. Similarities and differences of EM and UL at their incipient stages are enlightened with special emphasis on their gene networks, gene expression, and epigenetic regulation, of pathologic development. The analysis substantiates a new hypothesis postulating tumors as outgrowths of the stem cells with mesenchymal commitment lineage (mSC) which migrate from the endometrium/myometrium junctional zone of the uterus. Comparative analysis has revealed basic similarities of molecular pathogenesis of EM and UL suggesting molecular syntropy of both disorders. Peculiarities of the epigenetic landscape determining development of mSC may explain the existence of different clinical forms of EM and UL as well as their unique clinical manifestation. Some perspectives for practical and scientific application in EM and UL studies of this new hypothesis are outlined.

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Differential expression of microRNA species in human uterine leiomyoma versus normal myometrium

Abstract: Our findings indicate that miRNAs are differentially expressed between human leiomyoma and matched myometrium. Given this differential expression, miRNAs may play a role in the pathogenesis of uterine leiomyoma and may serve as future therapeutic targets for the treatment of these tumors.

Cited by 118 publications

References 27 publications

MicroRNA Expression and Regulation in Mouse Uterus during Embryo Implantation

MicroRNA Expression and Regulation in Mouse Uterus during Embryo Implantation

The Mechanism and Function of Epigenetics in Uterine Leiomyoma Development

Comparative systems genetics view of endometriosis and uterine leiomyoma: Two sides of the same coin?

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