MicroRNA Induction of Fatal Differentiation Programs is a Context-selective Vulnerability in Ovarian Cancer Cells [miRNA]
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Michael White
PROVIDER: E-GEOD-67329 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2015-03-27 | E-GEOD-67330 | 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 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
2015-03-27 | GSE67329 | GEO
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:Background: MicroRNAs (miRNAs) are small regulatory RNAs that are implicated in cancer pathogenesis and have recently shown promise as blood-based biomarkers for cancer detection. Epithelial ovarian cancer is a deadly disease for which improved outcomes could be achieved by successful early detection and enhanced understanding of molecular pathogenesis that leads to improved therapies. A critical step toward these goals is to establish a comprehensive view of miRNAs expressed in epithelial ovarian cancer tissues as well as in normal ovarian surface epithelial cells. Methodology: We used massively parallel pyrosequencing (i.e., M-bM-^@M-^\454 sequencingM-bM-^@M-^]) to discover and characterize novel and known miRNAs expressed in primary cultures of normal human ovarian surface epithelium (HOSE) and in tissue from three of the most common histotypes of ovarian cancer. Deep sequencing of small RNA cDNA libraries derived from normal HOSE and ovarian cancer samples yielded a total of 738,710 high-quality sequence reads, generating comprehensive digital profiles of miRNA expression. Expression profiles for 498 previously annotated miRNAs were delineated and we discovered six novel miRNAs and 39 candidate miRNAs. A set of 124 miRNAs was differentially expressed in normal versus cancer samples and 38 miRNAs were differentially expressed across histologic subtypes of ovarian cancer. Taqman qRT-PCR performed on a subset of miRNAs confirmed results of the sequencing-based study.
2009-03-12 | E-GEOD-15190 | biostudies-arrayexpress
Project description:We investigated whether levels of serum microRNAs (miRNAs) could discriminate women with high-grade serous ovarian epithelial cancer (SEOC) from age matched healthy volunteers. miRNA expression profiling was performed on 4 SEOC cell lines and normal human ovarian surface epithelial cells (HOSE). miR-182, miR-200a, b and c were highly overexpressed in the SEOC cell lines. miR-103, miR-92a and miR-638 displayed relatively invariant expression and with RNU48, were assessed, as putative serum miRNA normalizers. The 7 miRNA and RNU48 were assessed in serum from SEOC patients (n = 30) and age-matched healthy volunteers (n = 32) by qRT-PCR following pre-amplification. No correlation between age and miRNA or RNU48 levels was observed (age range 30-79 years). miR-103 demonstrated the least variance and was chosen to normalize serum volume adjusted results. miR-200a, b and c were significantly elevated in SEOC serum (P = 0.002; 0.003; 0.0003 respectively) and a multivariate model was the best predictive classifier of SEOC (ROC-AUC = 0.806). A correlation between high miR-200b levels and residual macroscopic disease following cytoreductive surgery was identified (P = 0.006). Our results suggest that serum miR-200a, b and c may have utility as diagnostic biomarkers for SEOC. miRNA expression was arrayed in 1 human surface epithelial cells (HOSE) and 4 ovarian cancer cell lines (OV167, OV202, OVCAR-3, PE01). HOSE cells were run in triplicate (including 1 dye-swap). Ovarian cancer cell lines were run in duplicate (including 1 dye-swap).
2012-02-22 | E-GEOD-35951 | biostudies-arrayexpress
Project description:In order to determine the difference at the microRNA level of different ovarian tumor histotypes, we have performed a whole miRNA screening on 183 patients of grade 1 ovarian cancer. Additionally, we compared the miRNA profile of tumors with standard ovarian epithelial cells (HOSE).
2013-06-17 | E-MTAB-1067 | biostudies-arrayexpress
Project description:The source of IFN-γ in ovarian cancer microenvironment and its biological effect to the tumor cells is unclear. The immortalized human ovarian surface epithelial cell line, HOSE-E7/hTERT (HOSE) was treated with IFN-γ and expression microarray analysis was performed, and probes showing significantly higher values in IFN-γ-added group were termed â??IFN-γ signature genes (295 probes)â??. We then applied this signature to our ovarian cancer microarray data, which included 75 ovarian cancer clinical samples, by means of ss-GSEA. IFN-γ signature score was strongly correlated to the number of infiltrating CD4-positive or CD8-positive lymphocytes in the tumors. These data suggest that the IFN-γ in the ovarian cancer microenvironment is derived from lymphocytes, and an IFN-γ-rich microenvironment is strongly correlated to a lymphocyte-rich microenvironment. HOSE cells were incubated in 8 separate culture dishes, 4 dishes with and 4 dishes without 500 IU/ml recombinant human IFN-γ (R&D Systems) in the culture medium for 6 hours prior to the analysis.
2014-03-04 | E-GEOD-55510 | biostudies-arrayexpress
Project description:Ovarian cancer is the most lethal malignancy in the United States. In the year 2012, there will be an estimated 22,280 new cases and 15,500 deaths from ovarian cancer in the country (Siegel et al., 2012). While studies on ovarian cancer pathogenesis were mainly focused on the epithelial component of the tumor, understanding in the role of cancer associated fibroblasts (CAFs) in ovarian cancer progression is limited. We hypothesized that comparing the gene expression profiles of different components from laser capture microdissected ovarian tissue will allow us to identify an ovarian CAFs specific gene signature which accounts for the supportive role of CAFs in ovarian cancer progression. In this study, gene expression profiling was completed for 31 cancer stroma samples and 32 samples of epithelial component from high grade serous ovarian cancer patients. 8 microdissected normal ovarian stroma and 6 normal human ovarian surface epithelium (HOSE) samples were also included in the study. By comparing the expression data from cancer stroma against that from normal stroma, cancer cells and HOSE, we identified a set of differential expressed genes in ovarian CAFs which showed correlation with cancer patient survival. Further study on these genes can reveal their roles in ovarian cancer progression and pathogenesis. Ultimately, ovarian CAFs specified genes identified in this study may aid in the classification and enhancement of patient outcome. Transcriptome profiling analyses were performed on 31 laser microdissected cancer associated stroma samples, 32 epithelial tumor samples from high grade serous ovarian cancer patients, 8 microdissected normal ovarian stroma samples and 6 ovarian surface epthelium (HOSE) samples using the Affymetrix human genome U133 Plus 2.0 microarray.
2014-09-11 | E-GEOD-40595 | biostudies-arrayexpress