JNKinhibitors for the treatment of inflammation and endometriosis [epithelial cells]
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PROVIDER: PRJNA1220716 | ENA |
REPOSITORIES: ENA
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Project description:JNKinhibitors for the treatment of inflammation and endometriosis [stroma]
| PRJNA1220717 | ENA
Project description:Endometriosis is a common disease in women characterized by the growth of endometrial-like lesions at ectopic sites, associated with chronic pelvic pain and infertility. LINC01638 is a long non-coding RNA (lncRNA) that in several cancers has been implicated in the regulation of proliferation and epithelial-to-mesenchymal transition (EMT). Given that these processes are also important in endometriosis, we investigated the role of LINC01638 in this disease. We found that LINC01638 is upregulated in the epithelial layer of endometriosis lesions, and that knockdown of the gene in 12Z epithelial endometriosis cell line led to reduced proliferation, adhesion, migration and invasion. The reduction in proliferation was associated with increased p21 and p27 expression and G1 phase arrest of 12Z cells, showing that LINC01638 acts as an important epigenetic regulator of endometriosis epithelial cells cell cycle progression. Further, transcriptome analysis of LINC01638 control and knockdown cells revealed that a number of transcription factors associated with EMT are downregulated in the knockdown, including FOXC2, SNAI2, TWIST1 and ZEB1, along with the mesenchymal marker VIM. These genetic and phenotypic changes in 12Z knockdown cells were accompanied by a significant reduction in expression of cytoskeleton regulatory gene RHOB and an upregulation of HDAC1 expression. Chromatin immunoprecipitation analysis and HDAC1 inhibitory treatment in LINC01638 control and knockdown cells indicated that LINC01638 regulates RHOB expression via HDAC1 mediated regulation of its promoter acetylation. In vivo, RHOB is upregulated in the epithelial layer of endometriosis lesions compared to control and endometriosis patient eutopic endometrium, supporting a role in the disease. Together these results indicate that LINC01638 is an epigenetic regulator of pathogenesis of endometriosis promoting proliferation and EMT of endometriosis lesions.
2025-02-16 | GSE281916 | GEO
Project description:Mechanisms of immune dysregulation against established tumors are relatively well understood. Much less is known about the role of immune effectors against cancer precursor lesions. Endometrioid and clear cell ovarian tumors may partly derive from endometriosis, a commonly diagnosed chronic inflammatory disease. We performed here the most comprehensive immune gene expression analysis of pelvic inflammation in endometriosis and endometriosis-associated ovarian cancer (EAOC). RNA was extracted from 120 paraffin tissue blocks comprising of normal endometrium (n=32), benign endometriosis (n=30), atypical endometriosis (n=15) and EAOC (n=43). Serous tumors (n=15) were included as non-endometriosis associated controls. The immune microenvironment was profiled using Nanostring and the nCounter® GX Human Immunology Kit, comprising probes for a total of 511 immune genes. Please note that 3 normal endometrium samples did not pass the array quality filtering and therefore excluded in the data analyses.
2015-01-07 | E-GEOD-57545 | biostudies-arrayexpress
Project description:Given the importance of menstrual blood in the pathogenesis of endometriosis and the multifunctional roles of menstrual mesenchymal stem cells (MenSCs) in regenerative medicine, this issue has gained prominence in the scientific community. Moreover, recent reviews highlight how robust the integrated assessment of omics data is for endometriosis. To our knowledge, no study has applied the multi-omics approaches to endometriosis MenSCs. It is a case-control study at a university-affiliated hospital. MenSCs transcriptome and proteome data were obtained by RNA-seq and UHPLC- MS/MS detection. Among the differentially expressed proteins and genes, we emphasize ATF3, ID1, ID3, FOSB, SNAI1, NR4A1, EGR1, LAMC3, and ZFP36 genes and MT2A, TYMP, COL1A1, COL6A2, and NID2 proteins that were already reported in the endometriosis. Our functional enrichment analysis reveals integrated modulating signaling pathways such as epithelial-mesenchymal transition (↑) and PI3K signaling via AKT to mTORC1 (↓in proteome), mTORC1 signaling, TGF beta signaling, TNFA signaling via NFkB, and response to hypoxia via HIF1A targets (↑in transcriptome). Our findings highlight primary changes in the endometriosis MenSCs, suggesting that the chronic inflammatory endometrial microenvironment can modulate these cells, providing opportunities for endometriosis etiopathogenesis. Moreover, they identify challenges for future research leveraging knowledge for regenerative and precision medicine in endometriosis.
2023-03-11 | PXD037033 | Pride
Project description:Endometriosis is a common, chronic inflammatory condition that frequently results in pain and infertility and is estimated to affect 6–10% of women of reproductive age. However, the mechanisms underlying the induction of inflammation in endometriosis remain unclear. Here, we identified that ectopic endometrial T-cell-derived active interleukin (IL)-16 acts as an inflammation-driving cytokine in endometriosis. Furthermore, we found that in ectopic endometrial T cells, the activation of IL-16 requires iron overload-induced caspase-3 activity and that the release of active IL-16 is reliant on GSDME-mediated pyroptosis. These observations suggest that active IL-16 may represent a promising target in the treatment of endometriosis.
2024-04-10 | GSE229735 | GEO
Project description:Endometriosis is a common gynecological disorder characterized by ectopic growth of endometrium outside the uterus and associated with chronic pain and infertility. We investigated the role of LINC01133 in endometriosis, an lncRNA that has been implicated in several types of cancer. We found that LINC01133 is upregulated in ectopic endometriosis lesions. As expression appeared higher in the epithelial endometrial layer, we performed an siRNA knockdown of LINC01133 in an endometriosis epithelial cell line. Phenotypic assays indicated that LINC01133 may promote proliferation and suppress cellular migration, and affect the cytoskeleton and morphology of the cells. Gene ontology analysis of differentially expressed genes detected by RNA sequencing indicated that cell proliferation and migration pathways were affected in line with the observed phenotype. We validated upregulation of p21 and downregulation of cyclin at the protein level, which together with DNA FACS analysis indicated that the observed effects on cellular proliferation may be due to changes in cell cycle progression. Further, we validated upregulation of the protein kinase TESK1 at the protein level, and found a corresponding increased phosphorylation and therefore inactivation of the actin severing protein Cofilin, which may explain changes in the cytoskeleton and cellular migration. These results indicate that LINC01133 upregulation is associated with endometriosis, which may be due to its effects on genes involved in the cellular proliferation and migration pathways.
2021-08-23 | GSE174741 | GEO
Project description:LINC01638 promotes epithelial-to-mesenchymal transition in endometriosis epithelial cells by upregulating RHOB via HDAC1 suppression
| PRJNA1186174 | ENA
Project description:We performed gene expression analysis human peritoneal endometriosis lesions, eutopic endometrium from endometriosis patients and peritoneum form endometriosis patients.The goal of the study was to analyse gene expression differences between peritoneal endometriosis lesion and eutopic endometrium and peritoneal endometriosis lesion and peritoneum.
2012-12-06 | E-MTAB-694 | biostudies-arrayexpress
Project description:We profiled transcriptomes of >370,000 individual cells from endometriomas (n=8), endometriosis (n=28), eutopic endometrium (n=10), unaffected ovary (n=4) and endometriosis-free peritoneum (n=4) to create a cellular atlas of endometrial-type epithelial cells, stromal cells, and microenvironmental cell populations across tissue sites.
2022-10-11 | GSE213216 | GEO
Project description:Mechanisms of immune dysregulation against established tumors are relatively well understood. Much less is known about the role of immune effectors against cancer precursor lesions. Endometrioid and clear cell ovarian tumors may partly derive from endometriosis, a commonly diagnosed chronic inflammatory disease. We performed here the most comprehensive immune gene expression analysis of pelvic inflammation in endometriosis and endometriosis-associated ovarian cancer (EAOC).
2015-01-07 | GSE57545 | GEO