Epigenome analysis of uterin leiomyoma and myometrium with or without leiomyoma
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Ryo Maekawa
PROVIDER: E-GEOD-45189 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Profiles of genome-wide DNA methylation were investigated in leiomyomas and in myometrium with and without leiomyomas. Profiles of DNA methylation in the myometrium with and without leiomyomas were quite similar while those in leiomyomas were distinct. Bisulphite converted DNA from the three uterine leiomyoma, three myometrium with leiomyoma and three myometrium without leiomyoma were hybridised to the Illumina infinium HumanMethylation450 BeadChip.
2013-09-01 | E-GEOD-45187 | biostudies-arrayexpress
Project description:Profiles of genome-wide DNA methylation were investigated in leiomyomas and in myometrium with and without leiomyomas. Profiles of DNA methylation in the myometrium with and without leiomyomas were quite similar while those in leiomyomas were distinct. Total RNA from the three uterine leiomyoma, three myometrium with leiomyoma and three myometrium without leiomyoma were analyzed with the Affymetrix GeneChip Mouse Gene 1.0 ST Array.
2013-09-01 | E-GEOD-45188 | biostudies-arrayexpress
Project description:Context: Progesterone is important physiologically and therapeutically to maintain uterine quiescence during pregnancy. It acts in part through controlling myometrial gene expression. Objective: To use expression microarray and qRT-PCR validation to determine the changes in gene expression induced by prolonged exposure to a synthetic progestogen. Design: Myometrial explants, obtained at elective Caesarean section (n=9 patients), were maintained in culture, under 0.6g tension, for 3 days in the presence or absence of medroxyprogesterone acetate (MPA, 100nM). Expression array was performed using Illumina human-8 v3 beadchip arrays. Approximately 30% of differentially expressed transcripts were validated in biological replicates (n=10) using qRT-PCR. Results: Transcripts from 114 genes were significantly differentially expressed. These were significantly enriched in inflammatory response (P=0.00001), growth factor activity (P=0.0004) and cytokine activity genes (P=0.008). 34 transcripts were validated using qRT-PCR using an additional independent sample set obtained from 10 further women. There was very close agreement in the fold changes obtained by array and qRT-PCR analysis (r2=0.9, P<0.0001). We confirmed significant down-regulation of a number of genes which have been well characterized as progesterone sensitive, such as IL1B, IL6, PTGS2 and GJA1. However, the top and 6th most down-regulated genes encoded two cytokines, IL11 and IL24, respectively, not previously implicated in mediating the effects of progesterone in myometrium. Both were validated by qRT-PCR (4.3-fold and 2.2-fold down-regulated, both P<0.001). Conclusions: Progestogens control expression of multiple genes in myometrium, including many with no previously recognised role, including IL11 and IL24. It is plausible that proteins encoded by some of these genes may have important, but as yet uncharacterized effects in controlling human parturition. 9 paired samples of human myometrium treated with MPA (10-7M) or vehicle
2011-06-08 | E-GEOD-22961 | biostudies-arrayexpress
Project description:Context: Increased uterine stretch appears to increase the risk of preterm labour, but the mechanism is unknown. Objectives: To identify a targetable mechanism mediating the effect of stretch on human myometrium. Design: Myometrial explants, prepared from biopsies obtained at elective caesarean delivery, were either studied acutely, or were maintained in prolonged culture (up to 65 h) under tension with either a 0.6 g or 2.4 g mass, and compared using in vitro contractility, whole genome array, and qRT-PCR. Results: Increased stretch for 24 or 65 h increased potassium-induced and oxytocin-induced contractility. Gene array identified 62 differentially expressed transcripts after 65 h exposure to increased stretch. Two probes for gastrin-releasing peptide (GRP), a known stimulatory agonist of smooth muscle, were among the top five up-regulated by stretch (3.4-fold and 2.0-fold). Up-regulation of GRP by stretch was confirmed in a separate series of 10 samples using qRT-PCR (2.8-fold, P = 0.01). GRP stimulated contractions acutely when added to freshly obtained myometrial strips in 3 out of 9 cases, but Western blot demonstrated expression of the GRP receptor in 9 out of 9 cases. Prolonged incubation of stretched explants in the GRP antagonists PD-176252 or RC-3095 (65 and 24 h respectively) significantly reduced potassium chloride and oxytocin-induced contractility. Conclusion: Stretch of human myometrium increases contractility and stimulates the expression of a known smooth muscle stimulatory agonist, GRP. Incubation of myometrium in GRP receptor antagonists ameliorates the effect of stretch. GRP may be a target for novel therapies to reduce the risk of preterm birth in multiple pregnancy. 9 paired samples of human myometrium cultured under low (0.6g) or high (2.4g) tension
2012-06-14 | E-GEOD-31329 | biostudies-arrayexpress
Project description:mircoRNA-200c (miR-200c) through repression of specific target genes has been associated with cellular transition, tumorigenesis and tissue fibrosis. We explored the expression and functional aspects of miR-200c in genesis of leiomyomas, benign uterine tumors with fibrotic characteristic. Gain-of function of miR-200c in isolated leiomyoma and myometrial smooth muscle cells (LSMC and MSMC) and leiomyosarcoma cell line (SKLM-S1) repressed ZEB1/ZEB2 mRNAs and proteins, with concurrent increase in E-cadherin (CDH1) and reduction in vimentin expression, phenotypic alteration and inhibition of MSMC and LSMC proliferation. We further validated TIMP2, FBLN5 and VEGFA as direct targets of miR-200c through interaction with their respective 3’UTRs, and other genes as determined by microarray analysis. Total RNA isolated from MSMC and LSMC following gain-of function of miR-200c was subjected to gene expression profiling using HumanHT-12 v4 Expression BeadChip (Illumina, Inc. San Diego, CA) consists of 47,000 oligonucleotide probe sets representing 28,688 transcripts.
2012-06-20 | E-GEOD-38817 | biostudies-arrayexpress
Project description:Uterine tissue is highly responsive to estrogen, which plays a mayor role in sympathetic innervation remodeling in myometrium; Microarrays were used to investigate which estrogen resposive myometrial proteins can be involved in innervation modulation Experiment Overall Design: Mature female rats were ovariectomized, than treated with estradiol benzoate or vechicle, myometrial samples were analyzed 6 or 24 h after treatment
2008-06-17 | E-GEOD-9117 | biostudies-arrayexpress
Project description:Study questionAre there differences in Mediator Complex Subunit 12 mutations (MED12) mutation, transcriptomics, and protein expression in uterine myometrium and leiomyomas of Black and White women?Summary answerRNA sequencing, tissue microarray, and immunohistochemistry data revealed that Black and White women have significant differences in their myometrium and leiomyoma profiles.What is known alreadyBlack women develop uterine leiomyoma earlier than White women, and are more likely to be anemic, have multiple tumors, undergo hysterectomy at an earlier age, have a higher uterine weight, and report very severe pelvic pain.Study design, size, durationUterine tissues were collected from premenopausal women undergoing hysterectomy or myomectomy at Northwestern University Prentice Women's Hospital (Chicago, IL) from 2010 to 2021. Tissues were collected from a total of 309 women, including from 136 Black women, 135 White women, and 38 women from other racial groups. A total of 529 uterine leiomyomas (290 from Black women, 184 from White women, and 55 from women of other racial groups) were subjected to molecular analysis. Leiomyoma and matched myometrium from a total of 118 cases including 60 Black women and 58 White women, were used for tissue microarrays, along with 34 samples of myometrium without leiomyoma from White women.Participants/materials, setting, methodsTissues from the above patient cohorts were analyzed by tissue microarray, immunohistochemistry, RNA sequencing, and mutation analysis.Main results and the role of chanceThe results indicated that leiomyoma from Black women have a higher rate of MED12 mutations (79.0%) than those from White women (68.5%) (*P ≤ 0.05). RNA-sequencing analysis in myometrium revealed differentially expressed genes (270 upregulated, 374 downregulated) dependent on race, wherein reactive oxygen species, hypoxia, and oxidative phosphorylation pathways were positively correlated with samples derived from Black patients. The levels of proteins associated with oxidative DNA damage and repair, 8-hydroxyguanosine (8-OHdG), 8-oxoguanine glycosylase (OGG1), heme oxygenase-1 (HO-1), and kelch-like ECH-associated protein 1 (KEAP1), were higher in leiomyoma and matched myometrium, particularly those from Black patients, compared to the control myometrium (with leiomyoma) (***P ≤ 0.001).Large scale dataThe datasets are available in the NCBI (The BioProject number: PRJNA859428).Limitations, reasons for cautionMyometrium without leiomyoma derived from White patients was used as a control in the tissue microarray analysis, as myometrium without leiomyoma from Black patients was not accessible in large numbers. The RNA sequencing was performed on myometrium tissue with leiomyoma present from 10 White and 10 Black women. However, one sample from a Black woman yielded low-quality RNA-sequencing data and was excluded from further analysis.Wider implications of the findingsWomen with symptomatic leiomyomas have a considerable loss in their quality of life. This study provides information on underlying genetic and molecular defects that may be necessary for future therapeutics targeted at leiomyomas.Study funding/competing interest(s)This work was supported by grants from NCI (R01CA254367) and NICHD (P01HD057877). The authors declare no conflict of interest.
| S-EPMC10068273 | biostudies-literature
Project description:Uterine fibroids are the most common benign tumor in women. The goal of this study was to investigate whether nicotinamide adenine dinucleotide phosphate oxidase (NOX), a major source of superoxide and subsequent oxidative stress, was differentially regulated in myometrium versus leiomyoma. Expression levels of NOXs1-5, dual oxidase (DUOX), DUOX2, NOX organizer (NOXO) 1, NOX activator 1, p47(phox), p67(phox), and p22(phox) were determined in cells treated with hypoxia by real-time reverse transcription-polymerase chain reaction, Western blot, and immunohistochemistry in tissues. Expression of NOX4 increased in fibroid compared to myometrial tissues and cells. The NOX2, DUOX1, and p67(phox) were higher while p22(phox) was lower in fibroid than that in myometrial cells. Hypoxia increased NOX4, DUOX1, and NOXO1 and decreased p22(phox) in myometrial and reduced DUOX1 in fibroid cells. The NOX1, NOX3, NOX5, and DUOX2 were undetectable. Fibroid cells are characterized by a unique NOX profile, which promotes a severe prooxidant state that may be responsible for their development. Targeting these subunits may be beneficial for future therapeutic interventions.
| S-EPMC5933080 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2013-09-01 | GSE45189 | GEO
Project description:Uterine leiomyoma are a common benign pelvic tumors composed of modified smooth muscle cells and a large amount of extracellular matrix (ECM). The proteoglycan composition of the leiomyoma ECM is thought to affect pathophysiology of the disease. To test this hypothesis, we examined the abundance (by immunoblotting) and expression (by quantitative real-time polymerase chain reaction) of the proteoglycans biglycan, decorin, and versican in leiomyoma and normal myometrium and determined whether expression is affected by steroid hormones and menstrual phase. Leiomyoma and normal myometrium were collected from women (n = 17) undergoing hysterectomy or myomectomy. In vitro studies were performed on immortalized leiomyoma (UtLM) and normal myometrial (hTERT-HM) cells with and without exposure to estradiol and progesterone. In leiomyoma tissue, abundance of decorin messenger RNA (mRNA) and protein were 2.6-fold and 1.4-fold lower, respectively, compared with normal myometrium. Abundance of versican mRNA was not different between matched samples, whereas versican protein was increased 1.8-fold in leiomyoma compared with myometrium. Decorin mRNA was 2.4-fold lower in secretory phase leiomyoma compared with proliferative phase tissue. In UtLM cells, progesterone decreased the abundance of decorin mRNA by 1.3-fold. Lower decorin expression in leiomyoma compared with myometrium may contribute to disease growth and progression. As decorin inhibits the activity of specific growth factors, its reduced level in the leiomyoma cell microenvironment may promote cell proliferation and ECM deposition. Our data suggest that decorin expression in leiomyoma is inhibited by progesterone, which may be a mechanism by which the ovarian steroids affect leiomyoma growth and disease progression.
| S-EPMC5933092 | biostudies-literature