LY75 ablation mediates mesenchymal-epithelial transition (MET) in epithelial ovarian cancer (EOC) cells associated with aberrant DNA methylation alterations implicated in EOC dissemination
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA596535 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10735773.fastq.gz | Fastqsanger.gz | |||
| SRR10735774.fastq.gz | Fastqsanger.gz | |||
| SRR10735775.fastq.gz | Fastqsanger.gz | |||
| SRR10735776.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 4 of 4 |
Similar Datasets
Project description:In epithelial ovarian cancer (EOC), acquisition of invasiveness is accompanied by the loss of the epithelial features and the gain of a mesenchymal phenotype, a process known as epithelial-mesenchymal transition (EMT). Understanding the regulation of cell behavior during EMT is crucial for identifying the molecular mechanisms of EOC dissemination. Previously we identified the mannose receptor LY75 as the cellular phenotype modulator. LY75 suppression induces the mesenchymal to epithelial transition (MET) in EOC cell lines with mesenchymal phenotype. In this study, we used the Reduced Representation Bisulfite Sequencing (RRBS) technology for a comprehensive analysis of DNA methylation alterations during LY75-mediated EMT in EOC cells. Three different comparison (M vs E) combinations were used for RRBS analysis, as further analysis of the sequencing data based on differentially methylated regions (DMRs) covering genes’ exons and promoter regions was indicative for about 10,000 genes displaying DMRs for each of the three experimental combinations. Consecutive Venn diagram analysis of the DMRs data from the of the three experimental combinations revealed 6666 genes, displaying common altered DMRs in their exons/promoter regions, following LY75-mediated EMT alterations in EOC cells. Based on the 6666 gene list, we further proceeded with a more stringent selection of genes displaying rather high degree (>70%) of methylation in their promoter regions and previously shown to be implicated in cancer-related EMT signaling. Our stringent selection retained 45 genes (see Supplemental Table 1E), as the DNA methylation status of the promoter regions of most of these genes was further validated by an alternative approach (BSP sequencing). Ten genes were finally selected, whose promoter DNA methylation pattern coincided with their mRNA and protein expression levels. Further in vitro and in vivo studies are warranted to more completely elucidate the functional implications of these 10 genes in ovarian tumorigenesis.
2020-03-30 | GSE142310 | GEO
Project description:Epithelial ovarian cancer (EOC) accounts for 4% of all cancers in women and is the leading cause of death from gynecologic malignancies. It is well established that cancer invasion and metastasis still represent the major causes of the failure of cancer treatment. Previously, we identified the mannose receptor LY75 (DEC205/CD205) gene as notably hypomethylated in high-grade (HG) serous epithelial ovarian tumors, compared to normal ovarian tissues. LY75 has been identified as a putative antigen-uptake receptor, which is expressed abundantly on dendritic cells, which are specialist antigen presenting cells to T lymphocytes for the initiation of an immune response. The implication of LY75 in EOC tumorigenesis is currently unknown. Here we show that LY75 is strongly overexpressed in HG serous EOC tumors as compared to normal ovarian tissue. Importantly, shRNA-mediated LY75 knockout in the mesenchymal EOC cells (SKOV3) led to mesenchymal to epithelial transition (MET), associated with overexpression of epithelial markers E-cadherin and EPCAM and loss of expression of mesenchymal markers Fibronectin, N-cadherin Snail1 and Twist1. In addition, LY75 suppression significantly inhibited EOC cell migration and invasion in vitro. However, LY75 knockdown led to enhanced tumor cell dissemination and significantly increased lethality in vivo, in xenograft model of advanced peritoneal EOC. Thus, our findings indicate that LY75 could play an essential role in the mesenchymal-to-epithelial transition (MET) of EOC cells and support the hypothesis that, while epithelial-to-mesenchymal transition (EMT) enables the invasiveness of tumor cells, a MET-associated epithelial phenotype could be essential for their metastatic colonization. To better understand the molecular mechanisms of LY75 gene action in epithelial ovarian cancer (EOC), we employed the Agilent Whole Human Genome microarrays, containing ~ 44,000 genes to identify global gene expression changes upon LY75 suppression in SKOV3 EOC cells. We compared the gene expression of the previously selected shRNA-mediated LY75-knockdown clones sh-S3 and sh-S6 against the corresponding control (ctrl) clone. The microarray experiments were performed in duplicates, as two hybridizations were carried out for each of the LY75-suppressing cell clone against the corresponding control, using a fluorescent dye reversal (dye-swap) technique.
2016-04-01 | E-GEOD-74711 | biostudies-arrayexpress
Project description:Epithelial ovarian cancer (EOC) accounts for 4% of all cancers in women and is the leading cause of death from gynecologic malignancies. It is well established that cancer invasion and metastasis still represent the major causes of the failure of cancer treatment. Previously, we identified the mannose receptor LY75 (DEC205/CD205) gene as notably hypomethylated in high-grade (HG) serous epithelial ovarian tumors, compared to normal ovarian tissues. LY75 has been identified as a putative antigen-uptake receptor, which is expressed abundantly on dendritic cells, which are specialist antigen presenting cells to T lymphocytes for the initiation of an immune response. The implication of LY75 in EOC tumorigenesis is currently unknown. Here we show that LY75 is strongly overexpressed in HG serous EOC tumors as compared to normal ovarian tissue. Importantly, shRNA-mediated LY75 knockout in the mesenchymal EOC cells (SKOV3) led to mesenchymal to epithelial transition (MET), associated with overexpression of epithelial markers E-cadherin and EPCAM and loss of expression of mesenchymal markers Fibronectin, N-cadherin Snail1 and Twist1. In addition, LY75 suppression significantly inhibited EOC cell migration and invasion in vitro. However, LY75 knockdown led to enhanced tumor cell dissemination and significantly increased lethality in vivo, in xenograft model of advanced peritoneal EOC. Thus, our findings indicate that LY75 could play an essential role in the mesenchymal-to-epithelial transition (MET) of EOC cells and support the hypothesis that, while epithelial-to-mesenchymal transition (EMT) enables the invasiveness of tumor cells, a MET-associated epithelial phenotype could be essential for their metastatic colonization.
2016-04-01 | GSE74711 | GEO
Project description:The molecular basis of epithelial ovarian cancer (EOC) dissemination is still poorly understood. We have previously identified the hydrogen peroxide-inducible clone-5 (Hic-5) gene as hypomethylated in high-grade (HG) serous EOC tumors, compared to normal ovarian tissues. Hic-5 is a focal adhesion scaffold protein and has been primarily studied for its role as a key mediator of TGF-β–induced epithelial-to-mesenchymal transition (EMT) in epithelial cells of both normal and malignant origin; however, its role in EOC has been never investigated. Here we demonstrate that Hic-5 is overexpressed in advanced EOC, and that Hic-5 is upregulated upon TGFβ1 treatment in the EOC cell line with epithelial morphology (A2780s), associated with EMT induction. However, ectopic expression of Hic-5 in A2780s induces alone EMT, accompanied with enhancement of their proliferation rate and migratory/invasive capacity and increased resistance to chemotherapeutic drugs. Moreover, Hic-5 knockdown in the EOC cell lines with mesenchymal morphology (SKOV3), was accompanied by induction of mesenchymal-to-epithelial transition (MET), followed by a reduction of their proliferative, migratory and invasive capacity, and increased drugs sensitivity in vitro and enhanced tumor cell colonization and metastatic growth in vivo. The modulation of Hic-5 expression in EOC cells resulted in altered regulation of numerous EMT-related canonical pathways and was indicative for a possible role of Hic-5 in controlling EMT through a RhoA/ROCK mediated mechanism. To our knowledge, this is the first report examining the role of Hic-5 in EOC, and its role in maintaining the mesenchymal phenotype of EOC cells independently of exogenous TGFβ1 treatment.
2017-10-22 | GSE98737 | GEO
Project description:We optimized a method previously developed to extract EVs from epithelial ovarian cancer (EOC) tissues and investigated whether cryopreservation of EOC tissues in clinical practice affects the phenotypes, contents, and biological functions of subsequently extracted EVs.
2023-05-10 | PXD039422 | Pride
Project description:NMuMG is an epithelial cell line that can be induced into EMT by TGF-β treatment or MET by TGF-β withdrawl. During EMT, several marker genes were downregulated/upregulated, which is consistent with its mesenchymal phenotype. Transcription factors that are regulated during EMT and its reverse process MET are candidate genes for the regulations of the EMT marker genes.
2013-07-26 | GSE48204 | GEO
Project description:Gene expression and mutation profiles in advanced-stage epithelial ovarian cancer (EOC)
| PRJNA1198945 | ENA
Project description:Epithelial ovarian cancer (EOC) is clinically heterogeneous, comprising different histological and biological subtypes. Multiple studies have implicated epithelial-mesenchymal transition (EMT), a biological process by which polarized epithelial cells convert into a mesenchymal phenotype, to contribute significantly to this molecular heterogeneity of EOC. From gene expression analyses of a collection of EMT-characterized EOC cell lines, we found that the expression of the transcription factor Grainyhead-like 2 (GRHL2) correlates with E-cadherin expression and the epithelial phenotype. EOC tumors with lower levels of GRHL2 are associated with the Mes (mesenchymal) molecular subtype and show poorer overall survival in patients. Here, we demonstrate that shRNA-mediated knockdown of GRHL2 in EOC cells with an epithelial phenotype resulted in EMT changes, with increased cell migration, invasion and motility. By ChIP-sequencing and gene expression microarray, we identified a variety of target genes regulated by GRHL2, including protein-coding and non-coding genes. Our data suggest that GRHL2 maintains the epithelial phenotype of EOC cells through the regulatory networks of miR-200b/a, ZEB1 and E-cadherin. These findings support GRHL2 as a crucial player in the molecular heterogeneity of EOC. 7 samples were analyzed (shNon control in duplicates; shGRHL2 #10 in duplicates, shGRHL2 #12 in triplicates)
2016-02-25 | E-GEOD-71017 | biostudies-arrayexpress
Project description:NMuMG is an epithelial cell line that can be induced into EMT by TGF-β treatment or MET by TGF-β withdrawl. During EMT, several marker genes were downregulated/upregulated, which is consistent with its mesenchymal phenotype. Transcription factors that are regulated during EMT and its reverse process MET are candidate genes for the regulations of the EMT marker genes. NMuMG cells treated with vehicle, TGF-β for 11 days, or 11days of TGF-β treatment followed by TGF-β withdrawl for another 13 days. RNA from these 3 conditions of NMuMG were extracted and subject to microarray analysis
2013-07-26 | E-GEOD-48204 | biostudies-arrayexpress
Project description:Epithelial ovarian cancer (EOC) is clinically heterogeneous, comprising different histological and biological subtypes. Multiple studies have implicated epithelial-mesenchymal transition (EMT), a biological process by which polarized epithelial cells convert into a mesenchymal phenotype, to contribute significantly to this molecular heterogeneity of EOC. From gene expression analyses of a collection of EMT-characterized EOC cell lines, we found that the expression of the transcription factor Grainyhead-like 2 (GRHL2) correlates with E-cadherin expression and the epithelial phenotype. EOC tumors with lower levels of GRHL2 are associated with the Mes (mesenchymal) molecular subtype and show poorer overall survival in patients. Here, we demonstrate that shRNA-mediated knockdown of GRHL2 in EOC cells with an epithelial phenotype resulted in EMT changes, with increased cell migration, invasion and motility. By ChIP-sequencing and gene expression microarray, we identified a variety of target genes regulated by GRHL2, including protein-coding and non-coding genes. Our data suggest that GRHL2 maintains the epithelial phenotype of EOC cells through the regulatory networks of miR-200b/a, ZEB1 and E-cadherin. These findings support GRHL2 as a crucial player in the molecular heterogeneity of EOC.
2016-02-25 | GSE71017 | GEO