Similar Datasets
Project description:NFAT5-sensitive upregulation of COX2 in endometrial ishikawa cells
| PRJNA554697 | ENA
Project description:Nuclear factor of activated T cells 5 (NFAT5) and cyclooxygenase 2 (COX2; PTGS2) both participate in diverse pathologies including cancer progression. However, the biological role of the NFAT5-COX2 signaling pathway in human endometrial cancer has remained elusive. The present study explored whether NFAT5 is expressed in endometrial tumors and if NFAT5 participates in cancer progression. To gain insights into the underlying mechanisms, NFAT5 protein abundance in endometrial cancer tissue was visualized by immunohistochemistry and endometrial cancer cells (Ishikawa and HEC1a) were transfected with NFAT5 or with an empty plasmid. As a result, NFAT5 expression is more abundant in high-grade than in low-grade endometrial cancer tissue. RNA sequencing analysis of NFAT5 overexpression in Ishikawa cells upregulated 37 genes and downregulated 20 genes. Genes affected included cyclooxygenase 2 and hypoxia inducible factor 1α (HIF1A). NFAT5 transfection and/or treatment with HIF-1α stabilizer exerted a strong stimulating effect on HIF-1α promoter activity as well as COX2 expression level and prostaglandin E2 receptor (PGE2) levels. Our findings suggest that activation of NFAT5-HIF-1α-COX2 axis could promote endometrial cancer progression.
| S-EPMC11012216 | biostudies-literature
Project description:Interventions: Case vs control:No
Primary outcome(s): High-throughput sequencing
Study Design: Case-Control study
| 2676067 | ecrin-mdr-crc
Project description:BackgroundThe link between environmental estrogen exposure and defects in the female reproductive tract is well established. The phytoestrogen genistein is able to modulate uterine estrogen receptor (ER) activity, and dietary exposure is associated with uterine pathologies. Regulation of stress and immune functions by the glucocorticoid receptor (GR) is also an integral part of maintaining reproductive tract function; disruption of GR signaling by genistein may also have a role in the adverse effects of genistein.ObjectiveWe evaluated the transcriptional response to genistein in Ishikawa cells and investigated the effects of genistein on GR-mediated target genes.MethodsWe used Ishikawa cells as a model system to identify novel targets of genistein and the synthetic glucocorticoid dexamethasone through whole genome microarray analysis. Common gene targets were defined and response patterns verified by quantitative real-time reverse-transcription polymerase chain reaction. The mechanism of transcriptional antagonism was determined for select genes.ResultsGenistein regulated numerous genes in Ishikawa cells independently of estradiol, and the response to coadministration of genistein and dexamethasone was unique compared with the response to either estradiol or dexamethasone alone. Furthermore, genistein altered glucocorticoid regulation of GR target genes. In a select set of genes, co-regulation by dexamethasone and genistein was found to require both GR and ERα signaling, respectively.ConclusionsUsing Ishikawa cells, we observed that exposure to genistein resulted in distinct changes in gene expression and unique differences in the GR transcriptome.
| S-EPMC4286279 | biostudies-literature
Project description:To explain the possible molecular mechanism underlying the oncogenic roles of IGF2BP3 in EC, we employed RNA immunoprecipitation (RIP) assays to identify the lncRNAs involved in the regulation of IGF2BP3 function. RIP experiments, high-throughput sequencing and data analysis were performed by Seqhealth Tech (Wuhan, China). RIP assays were carried out on Ishikawa cells. The cells were lysed, and the lysis samples for immunoprecipitation reactions were incubated with anti-IGF2BP3 antibody (ab177477, Abcam, USA) or rabbit IgG (Cell Signaling Technology). The library products were enriched, quantified and finally sequenced on the Illumina PE150 platform.One hundred ninety-one candidates as IGF2BP3-interacting lncRNAs were identified in the RIP-seq results.
2022-03-16 | GSE198620 | GEO
Project description:Interventions: left hemicolectomy:None;right hemicolectomy:None;sigmoid resection:None;radical rectal cancer:None;low rectal resection with prophylactic ileostomy:None
Primary outcome(s): Fecal high-throughput sequencing;Fecal Metabolomics;immunomics
Study Design: Factorial
| 85716 | ecrin-mdr-crc
Project description:GOLPH3 was silenced in human endometrial stromal cells (hESCs), and the transcriptome data (RNA-seq) by GOLPH3 knockdown (siGOLPH3) was obtained by high-throughput sequencing technology,
2022-10-12 | GSE215155 | GEO
Project description:Increased activity and excitability (sensitisation) of a series of molecules including the transient receptor potential ion channel, vanilloid subfamily, member 1 (TRPV1) in pain-sensing (nociceptive) primary sensory neurons are pivotal for developing pathological pain experiences in tissue injuries. TRPV1 sensitisation is induced and maintained by two major mechanisms; post-translational and transcriptional changes in TRPV1 induced by inflammatory mediators produced and accumulated in injured tissues, and TRPV1 activation-induced feed-forward signalling. The latter mechanism includes synthesis of TRPV1 agonists within minutes, and upregulation of various receptors functionally linked to TRPV1 within a few hours, in nociceptive primary sensory neurons. Here, we report that a novel mechanism, which contributes to TRPV1 activation-induced TRPV1-sensitisation within ~ 30 min in at least ~ 30% of TRPV1-expressing cultured murine primary sensory neurons, is mediated through upregulation in cyclooxygenase 2 (COX2) expression and increased synthesis of a series of COX2 products. These findings highlight the importance of feed-forward signalling in sensitisation, and the value of inhibiting COX2 activity to control pain, in nociceptive primary sensory neurons in tissue injuries.
| S-EPMC7876133 | biostudies-literature
Project description:Hormone therapy serves as a primary choice for fertility preservation and is also considered for advanced and recurrent cases with endometrial cancer. While a number of patients fail to respond favorably to hormone treatments. In order to explore the mechanisms underpinning hormone resistance, Here we constructed a whole-genome library for EAC cell lines using the CRISPR-Cas9 system and performed high-throughput sequencing after medroxyprogesterone treatment in this study. For CRISPR screening, ishikawa cells were infected pooled GeCkov2 lentiviral library with functional MOI of 0.3. Genomic DNA from each group was isolated and amplified by PCR. The PCR products were purified and subjected to NGS by using the Novaseq 6000-PE150 platform. After 48h of puromycin selection, the cells were divided into three groups, the baseline group cells were collected and frozen at -80 degree centigrade, the control group cells were treated with DMSO for 10 days while the MPA group cells were treated with 15 μM MPA for 10 days.
2024-02-12 | GSE241070 | GEO
Project description:Understanding the molecular underpinnings of chemoresistance is vital to design therapies to restore chemosensitivity. In particular, metadherin (MTDH) has been demonstrated to have a critical role in chemoresistance. Over-expression of MTDH has recently been implicated in poor clinical outcome in breast cancer, neroblastoma, hepatocellular carcinoma and prostate cancer. In this present study, we focused on the therapeutic benefit of MTDH depletion to restore sensitivity to cell death mediated by a combinatorial therapy of tumor necrosis factor-alpha-related apoptosis-inducing ligand (TRAIL), which promotes death of cancerous cells of the human reproductive tract, and histone deacetylase (HDAC) inhibitors, which have been shown to increase sensitivity of cancer cells to TRAIL-induced apoptosis. Our data indicate that depletion of MTDH in endometrial cancer cells results in sensitization of cells that were previously resistant to cell death mediated by combinatorial treatment with TRAIL and HDAC inhibitor LBH589. MTDH was found to be involved in G2/M checkpoint regulation in response to LBH589 alone or LBH589 in combination with TRAIL, suggesting that MTDH functions at the cell cycle checkpoint to accomplish resistance.Using microarray technology, we identified 57 downstream target genes of MTDH, including Calbindin 1 and Galectin 1, which may contribute to MTDH-mediated resistance to combinatorial TRAIL and HDAC inhibitor targeted therapy. Inhibition of PDK1,AKT phosphorylation and increase Bim expression and XIAP degradation may result in sensitivity to cell death induction in MTDH depleted Hec50co cells by TRAIL and LBH 589 combination treatment. These findings indicate that depletion of MTDH is a potentially novel avenue for effective cancer therapy. The microarray was performed on three biological triplicates as well as three experimental triplicates of stable knockdown and control cells. MTDH was knocked down using a shRNA.
| S-ECPF-GEOD-27828 | biostudies-other