Differential Expression of Super-enhancer-associated Long Non-coding RNAs in Uterine Leiomyomas
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PROVIDER: PRJNA795789 | ENA |
REPOSITORIES: ENA
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Project description:Arraystar SE-lncRNAs Arrays was used to systematically profile the differentially expressed SE-lncRNAs along with corresponding SE-regulated protein coding genes from eight leiomyomas and paired myometrium. The analysis indicated 7680 SE-lncRNAs were expressed, of which 721 SE-lncRNAs were increased, while 247 SE-lncRNAs were decreased by 1.5-fold or greater in leiomyoma. Thirteen novel SE-lncRNAs and their corresponding protein coding genes were selected, and their expression was confirmed in eighty-one paired leiomyoma tissues by quantitative real-time PCR. The thirteen pairs of SE-lncRNAs and their corresponding protein coding genes included RP11-353N14.2/CBX4, SOCS2-AS1/SOCS2, RP1-170O19.14/HOXA11, CASC15/PRL, EGFLAM-AS1/EGFLAM, RP11-225H22/NEURL1, RP5-1086K13.1/CD58, AC092839.3/SPTBN1, RP11-69I8.3/CTGF, TM4SF1-AS1/TM4SF1, RP11-373D23/FOSL2, RP11-399K21.11/COMTD1 and CTB-113P19.1/SPARC. Collectively, our results indicate that the differential expression of SE in fibroids is another mechanism contributing to dysregulation of protein coding genes in fibroids.
2022-01-11 | GSE193320 | GEO
Project description:The objective of this study was to elucidate the expression profile of coding RNA transcripts in leiomyomas with and without MED12 mutation and their paired myometrium.
2023-03-01 | GSE224991 | GEO
Project description:Insulin-like growth factor 1 (IGF1) is primarily synthesized in and secreted from the liver; however, estrogen (E2), through E2 receptor α (ERα), increases uterine Igf1 mRNA levels. Previous ChIP-Seq analyses of the murine uterus have revealed a potential enhancer region distal from the Igf1 transcription start site (TSS) with multiple E2-dependent ERα-binding regions. Here, we show E2-dependent super enhancer–associated characteristics and suggest contact between the distal enhancer and the Igf1 TSS. We hypothesized that this distal super-enhancer region controls E2-responsive induction of uterine Igf1 transcripts. We deleted 430 bp, encompassing one of the ERα-binding sites, thereby disrupting interactions of the enhancer with gene-regulatory factors. As a result, E2-mediated induction of mouse uterine Igf1 mRNA is completely eliminated, whereas hepatic Igf1 expression remains unaffected. This highlights the central role of a distal enhancer in the assembly of the factors necessary for E2-dependent interaction with the Igf1 TSS and induction of uterus-specific Igf1 transcription. Of note, loss of the enhancer did not affect fertility or uterine growth responses. Deletion of uterine Igf1 in a PgrCre;Igf1f/f model decreased female fertility, but did not impact the E2-induced uterine growth response. Moreover, E2-dependent activation of uterine IGF1 signaling was not impaired by disrupting the distal enhancer or by deleting the coding transcript. This indicated a role for systemic IGF1, suggested that other growth mediators drive uterine response to E2, and that uterine-derived IGF1 is essential for reproductive success. Our findings elucidate the role of a super enhancer in Igf1 regulation and uterine growth.
2019-05-08 | GSE125972 | GEO
Project description:Human uterine leiomyomas (ULM) are characterized by dysregulation of a large number of genes and non-coding regulatory microRNAs. In order to identify microRNA::mRNA associations relevant to ULM pathogenesis, we examined global correlation patterns between the altered microRNA expression and the predicted target genes in leiomyomas and matched myometria. We found that some but not all of the predicted and inversely correlated target genes in ULMs can be directly regulated by microRNAs in vitro. Our findings provide a broad overview of molecular events underlying the tumorigenesis of uterine leiomyoma and identify select genetic and regulatory events that alter microRNA expression and may play important roles in ULM pathobiology by positively regulating tumor growth while maintaining the non-invasive character of ULMs Keywords: Differential gene expression Paired normal (myometrium) and tumor (ULM) samples derived from 5 patients were used
2010-07-24 | E-GEOD-23112 | biostudies-arrayexpress
Project description:Uterine leiomyomas are the most common benign tumor in humans causing significant morbidity with vaginal bleeding, pelvic pressure and pain. Histologically, leiomyomas show a large degree of extracellular matrix disorganization. I am working with a colleague who recently found Notch pathway gene expression were clearly altered in fibroids (“Differential expression of the Notch signal transduction pathway: ligands, receptors and Numb in uterine leiomyomas vs. myometrium,” G. Christman, H. Tang, I. Ahmad, J. Stribley, Fertility and Sterility, Volume 88, Supp 1, S72, September 2007). Glycosaminoglycan expression was found to be over-expressed in uterine leiomyomas compared to myometrial samples (Fertility and Sterility, Vol 88 Supp 1, S106, September, 2007), but glycosyltransferase and glycosidase expression has not been reported. We have purified RNA samples from paired uterine leiomyoma and normal myometrium from a previous clinical study. Dr. Domino's laboratory hypothesis is that Notch pathway activation inhibits apoptosis in uterine leiomyomas leading to fibroid growth. Notch ligands are fucosylated glycans. The bulk of a fibroid is the extracellular matrix yet little has been studied on leiomyocyte expression of enzymes that model glycans in the extracellular matrix.
2011-04-29 | GSE28945 | GEO
Project description:Human uterine leiomyomas (ULM) are characterized by dysregulation of a large number of genes and non-coding regulatory microRNAs. In order to identify microRNA::mRNA associations relevant to ULM pathogenesis, we examined global correlation patterns between the altered microRNA expression and the predicted target genes in leiomyomas and matched myometria. We found that some but not all of the predicted and inversely correlated target genes in ULMs can be directly regulated by microRNAs in vitro. Our findings provide a broad overview of molecular events underlying the tumorigenesis of uterine leiomyoma and identify select genetic and regulatory events that alter microRNA expression and may play important roles in ULM pathobiology by positively regulating tumor growth while maintaining the non-invasive character of ULMs Keywords: Differential gene expression
2010-07-24 | GSE23112 | GEO
Project description:Uterine leiomyomas are the most common benign tumor in humans causing significant morbidity with vaginal bleeding, pelvic pressure and pain. Histologically, leiomyomas show a large degree of extracellular matrix disorganization. I am working with a colleague who recently found Notch pathway gene expression were clearly altered in fibroids (“Differential expression of the Notch signal transduction pathway: ligands, receptors and Numb in uterine leiomyomas vs. myometrium,” G. Christman, H. Tang, I. Ahmad, J. Stribley, Fertility and Sterility, Volume 88, Supp 1, S72, September 2007). Glycosaminoglycan expression was found to be over-expressed in uterine leiomyomas compared to myometrial samples (Fertility and Sterility, Vol 88 Supp 1, S106, September, 2007), but glycosyltransferase and glycosidase expression has not been reported. We have purified RNA samples from paired uterine leiomyoma and normal myometrium from a previous clinical study. Dr. Domino's laboratory hypothesis is that Notch pathway activation inhibits apoptosis in uterine leiomyomas leading to fibroid growth. Notch ligands are fucosylated glycans. The bulk of a fibroid is the extracellular matrix yet little has been studied on leiomyocyte expression of enzymes that model glycans in the extracellular matrix. RNA preparations of paired samples of excess human tissues from hysterectomies, with two different groups normal myometrium, and leiomyoma tumors were sent to Microarray Core (E). The RNA was amplified, labeled, and hybridized to GLYCO_v3 microarrays.
2011-04-29 | E-GEOD-28945 | biostudies-arrayexpress
Project description:MicroRNAs (miRNAs) are a class of small, non-coding RNAs. MiRNAs regulate developmental activity and may be aberrantly expressed in human diseases, including cancer. Expression of miRNAs is tissue or organ specific. Human uterine leiomyomas (ULMs) are the most common neoplasms of women, characterized by the ovarian sex hormone dependence, worse morbidity in black women and genetic heterogeneity. The high incidence of the disease may be associated with developmental defects in uteri. In this study, we examined miRNA expression in 55 ULMs with matched myometrium using spotted microarray platform. Keywords: Disease state analysis
2007-04-15 | GSE5244 | GEO
Project description:Estrogen receptor α (ERα) modulates gene expression through interactions with enhancer regions of chromatin that are frequently distal from the promoters of estrogen regulated genes. Active chromatin enriched “super-enhancer” (SE) regions, mainly described in in vitro culture systems, often control production of key cell type determining transcription factors. Here, we define ERα binding super-enhancers in vivo within hormone responsive uterine tissue. SE are already formed prior to estrogen exposure at the onset of puberty. The SE encode critical developmental factors including Rara and Hoxd. Using chromosome conformation capture with high throughput sequencing (Hi-C) we demonstrate that most ERα-binding SE are located at a chromatin loop end and most uterine genes in loop ends associated with ERα-binding SEs are estrogen regulated. Although SE are formed prior to puberty, SE-associated genes acquire optimal ERα dependent expression after reproductive maturity, indicating estrogen impacts enhancer function subsequent to assembly. ERα-binding SE-associated genes impact key uterine functions mediated by estrogen, including TGFβ and LIF signaling pathways. This is the first identification of ERα-binding SE interactions underlying hormonal regulation of genes in uterine tissue and optimal development of estrogen response
2020-04-29 | GSE147843 | GEO
Project description:Our study seeks to identify genes differentially expressed between uterine leiomyomas and normal myometrial tissue. This series consists of samples derived from normal myometrium and uterine leiomyomas obtained from fibroid afflicted patients.Total RNA was extracted from samples, converted to biotin-labeled cRNA, hybridized to oligonucleotide arrays, and followed by model based expression analysis. In order to select differentially expressed genes of interest, dChip model-based expression analysis was employed. Significant genes were identified, utilizing the dChip software, as having an average fold change of > +1.5 or < -1.5 between leiomyoma and normal myometrium and p < 0.05. Under these conditions the 226 genes in the following list were identified. Keywords: other
2003-10-17 | GSE593 | GEO