MicroRNA Induction of Fatal Differentiation Programs is a Context-selective Vulnerability in Ovarian Cancer Cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Michael White
PROVIDER: E-GEOD-67330 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Analysis of gene expression in ovarian cancer cells with and without overexpression of the miRNA mir-124 which will provide data about genes possibly directly regulated by miR-124. Also, analysis of gene expression in ovarian cancer cells with and without knockdown of the homeodomain transcription factor SIX4 (a target of miR-124) which will provide data about genes possibly directly regulated by SIX4 Total RNA was isolated from PEO4 cells transfected with miRNA mimic negative control (miNC), miR-124 mimic, siRNA negative control (siNC) oligo, or siRNA targeting the SIX4 gene (siSIX4) 72 hours post-transfection
2015-03-27 | E-GEOD-67328 | biostudies-arrayexpress
Project description:Analysis of gene expression in ovarian cancer cells with and without overexpression of the miRNA mir-124 which will provide data about genes possibly directly regulated by miR-124. Also, analysis of gene expression in ovarian cancer cells with and without knockdown of the homeodomain transcription factor SIX4 (a target of miR-124) which will provide data about genes possibly directly regulated by SIX4 Total RNA was isolated from PEO1 cells transfected with miRNA mimic negative control (miNC), miR-124 mimic, siRNA negative control (siNC) oligo, or siRNA targeting the SIX4 gene (siSIX4) 72 hours post-transfection
2015-03-27 | E-GEOD-67327 | biostudies-arrayexpress
Project description:Analysis of microRNA (miRNA) expression in ovarian cancer cell lines and human ovarian surface epithelium (HOSE) in order to identify differentially expressed miRNAs between cancer lines and HOSE Total RNA was isolated from cells 72 hours after plating
2015-03-27 | E-GEOD-67329 | biostudies-arrayexpress
Project description:Estrogen Receptor alpha (ERα), a nuclear receptor with transcriptional activity, is a master regulator of estrogen signaling, widely known as therapeutic target in hormone-responsive breast cancer (BC). Moreover, ERα is highly expressed in approximately 80% of High Grade Serous Ovarian Cancer (HGSOC), the most common epithelial ovarian carcinoma. Despite some promising clinical trials evaluating endocrine therapy in this type of tumor, the role of ERα is still unknown. Epigenetic changes, such as DNA methylation, are emerging as key contributing factors to carcinogenesis. Disruptor of telomeric silencing-1-like (DOT1L), the only known histone methyl transferase capable to produce H3K79 mono, di and tri-methylation, modulates ERα actions in hormone-responsive BC. Considering this evidence, ERα-DOT1L association was confirmed in ERα-positive OC cells, PEO1 and PEO4, by Co-IP. DOT1L pharmacological inhibition by EPZ004777 (EPZ) revealed the involvement of this epigenetic enzyme in cell proliferation, cell cycle progression and apoptosis. Transcriptome profiling after ICI (a Selective Estrogen Receptor Degrader) and EPZ treatment, in both cell lines, has underlined a deep impact of both compounds on ERα-modulated genes, including the down-regulation of ERα itself. On the other hand, functional analysis showed that commonly affected transcripts are involved in different cellular processes, such as cancer cell survival, chemoresistance and cell cycle progression. Moreover, ChIP-qPCR performed on ERα promoter highlighted ERα and DOT1L co-localization, both in PEO1 and in PEO4 cells, which was reduced after EPZ treatment, suggesting a role of this complex on receptor transcriptional activity. In addition, drug combination studies performed with EPZ and ICI showed an additive effect in cell growth inhibition. Taken together, these results suggest DOT1L as a potential therapeutic target in the treatment of OC.
2019-11-04 | E-MTAB-8198 | biostudies-arrayexpress
Project description:Basal-like carcinoma is a subtype of breast cancer that is characterized by poor prognosis and high intratumor heterogeneity. Using a basal-like breast epithelial line, we have identified two anti-correlated gene-expression programs that arise among single extracellular matrix (ECM)-attached cells during organotypic 3D culture. The first program contains TGFBR3, a high-affinity receptor for transforming growth factor β (TGFβ) and other related ligands. The second program contains the JUND transcription factor together with the basal-like marker, KRT5. By disrupting the TGFBR3 and JUND programs individually, we reveal an important circuit for 3D morphogenesis that is wired together by four negative-feedback loops. Computational modeling of this circuit showed that it could exhibit damped, antiphase oscillations when excited with small impulses of TGFβ-like ligand. We directly visualize the circuit's spontaneous dynamics in organotypic cultures by using live-cell imaging with engineered pathway reporters. Importantly, we show that the essence of the JUND-TGFBR3 expression circuit holds true in early basal-like tumors that heterogeneously express KRT5. Correlated JUND-KRT5 expression depends critically on contact with stromal ECM and local expression of tenascin C. This work illustrates how complex tumor heterogeneities can be deconstructed into intrinsic single-cell expression circuits that are modulated by the microenvironment. Gene expression analysis of outer ECM-attached vs. inner cells of MCF10A-5E clones grown in organotypic 3D culture at day 6. Total RNA was isolated from ~50 outer ECM-attached cells and ~50 inner cells, each separately microdissected from 8 micron sections of MCF10A structures at day 6 of morphogenesis. Total RNA was amplified in quadruplicate, and hybridized to HumanRef-8 v2.0 Expression BeadChips (Illumina).
2015-06-05 | E-GEOD-41527 | biostudies-arrayexpress
Project description:Direct conversion of fibroblasts to induced cardiomyocytes (iCMs) has great potential for regenerative medicine. Recent publications have reported significant progress, but the evaluation of reprogramming has relied upon non-functional measures such as flow cytometry for cardiomyocyte markers or GFP expression driven by a cardiomyocyte-specific promoter. The issue is one of practicality: the most stringent measures - electrophysiology to detect cell excitation and the presence of spontaneously contracting myocytes - are not readily quantifiable in the large numbers of cells screened in reprogramming experiments. However, excitation and contraction are linked by a third functional characteristic of cardiomyocytes: the rhythmic oscillation of intracellular calcium levels. We set out to optimize direct conversion of fibroblasts to iCMs with a quantifiable calcium reporter to rapidly assess functional transdifferentiation. We constructed a reporter system in which the calcium indicator GCaMP is driven by the cardiomyocyte-specific Troponin T promoter. Using calcium activity as our primary outcome measure, we compared several published combinations of transcription factors along with novel combinations in mouse embryonic fibroblasts. The most effective combination consisted of Hand2, Nkx2.5, Gata4, Mef2c, and Tbx5 (HNGMT). This combination is >50-fold more efficient than GMT alone and produces iCMs with cardiomyocyte marker expression, robust calcium oscillation, and spontaneous beating that persists for weeks following inactivation of reprogramming factors. HNGMT is also significantly more effective than previously published factor combinations for the transdifferentiation of adult mouse cardiac fibroblasts to iCMs. Quantification of calcium function is a convenient and effective means for the identification and evaluation of cardiomyocytes generated by direct reprogramming. Using this stringent outcome measure, we conclude that HNGMT produces iCMs more efficiently than previously published methods. Mouse embryonic fibroblasts were treated with different combinations of transcription factors to drive transdifferentiation to induced cardiomyocytes (iCMs). Putative iCMs were enriched by zeocin selection. Zeocin resistance was conferred to iCMs via the TroponinT-GCaMP5-Zeo lentiviral reporter.
2013-04-22 | E-GEOD-45274 | biostudies-arrayexpress
Project description:This study tested the hypothesis that mRNA expression profiles change in the muscular type rat saphenous artery during early postnatal development. To explore this, we performed mRNA microarray analysis on muscular type saphenous arteries of young (10-12 days) and adult (2-3 months) rats. For one sample four saphenous arteries from 2 young animals (n = 4 samples per group) or two saphenous arteries from one adult animal (n = 4 samples per group) were used to profile mRNA (n = 8; GeneChip® Rat Gene 1.0) expression changes during the muscular type rat saphenous artery during early postnatal development. In this study, 10-12 days old (“young”) and 2 - 3 months old (“adult”) male Wistar rats.
2015-04-30 | E-GEOD-60961 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2015-04-30 | E-GEOD-60963 | biostudies-arrayexpress
Project description:This study tested the hypothesis that miRNA expression profiles change in the muscular type rat saphenous artery during early postnatal development. To explore this, we performed miRNA microarray analysis on muscular type saphenous arteries of young (10-12 days) and adult (2-3 months) rats. For one sample four saphenous arteries from 2 young animals (n = 4 samples per group) or two saphenous arteries from one adult animal (n = 4 samples per group) were used to profile miRNA (n = 8; GeneChip® miRNA 3.0) expression changes during the muscular type rat saphenous artery during early postnatal development. In this study, 10-12 days old (“young”) and 2 - 3 months old (“adult”) male Wistar rats were used.
2015-04-30 | E-GEOD-60962 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the following subset Series: GSE25146: Changes in gene expression in AGS cells in response to Helicobacter pylori lipopolysaccharide GSE25147: Changes in gene expression in MKN45 cells in response to Helicobacter pylori lipopolysaccharide GSE25148: Changes in gene expression in HEK-TLR2 cells in response to Helicobacter pylori lipopolysaccharide Refer to individual Series
2011-01-12 | E-GEOD-25155 | biostudies-arrayexpress