Aberrant overexpression of TGF-β2 induces epithelial-mesenchymal transition in adenomyosis with β-catenin activation.
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE88911 | GEO | 2016/10/19
SECONDARY ACCESSION(S): PRJNA349054
REPOSITORIES: GEO
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Project description:Aberrant overexpression of TGF-β2 induces epithelial-mesenchymal transition in adenomyosis with β-catenin activation.
| PRJNA349054 | ENA
Project description:m6A-mRNA&lncRNA Epitranscriptomic Microarray of primary mouse RPE cells comparing control untreated RPE cells with RPE cells treated with TGF-β2 at a concentration of 10 ng/ml. The goal was to determine the effects of RNA m6a methylation on primary mouse RPE cells undergoing epithelial-mesenchymal transition induced by TGF-β2.
2021-06-26 | GSE178946 | GEO
Project description:Extracellular pH (pHe) is lower in many tumors than in the corresponding normal tissue. Acidic tumor microenvironment has been shown to facilitate epithelial mesenchymal transition (EMT) and tumor metastasis, while the mechanisms underlying tumor acidic microenvironment-induced tumor cell metastasis remain undefined. Here, we aimed to investigate the tumor metastasis and the EMT by acidic microenvironment and to explore their mechanisms and clinical significance in lung cancer. Results showed that acidic pHe remarkably enhanced invasion ability of lung cells accompanying with increased mesenchymal and decreased epithelial markers. Moreover, acidic pHe triggered the inhibition of microRNA-7 (miR-7) expression and activation of TGF-β2/SMAD signaling. Mechanistic studies showed that TGF-β2 is a direct potential target gene of miR-7, and acidity-induced metastasis could be abolished by treatment with a TGFβRI inhibitor, anti-TGF-β2 antibody and miR-7 mimic, respectively. The clinical samples further revealed that miR-7 was decreased in lung tissues and antagonistically correlated with TGF-β2 expression, associating with overall survival and metastasis. In conclusion, our study indicated that acidic pHe showed enhanced invasive potential, and enhanced potential to develop experimental metastases by a novel mechanism involving tumor acidic microenvironment-induced regulation of miR-7/TGF-β2/SMAD axis. Our findings suggest that the possibility that pHe of the primary tumor may be an important prognostic parameter for lung cancer patients merit clinical investigation. Moreover, miR-7 may serve as prognostic molecular marker and a novel therapeutic target for lung cancer.
2022-04-01 | PXD016524 | Pride
Project description:Adenomyosis mostly occurs in the females with reproductive age, and the pathogenesis is not clear. If we want to improve the diagnosis and treatment of adenomyosis, we must fully understand the specific molecular mechanism of adenomyosis. The Arraystar Human m6a-mRNA&lncRNA Epitranscriptomic microarray analysis was performed on endometrial specimens of 3 patients in the human adenomyosis group and 3 patients in the normal control group to compare and screen the m6A marker of adenomyosis, providing reference for clinical treatment.
2022-10-06 | GSE214850 | GEO
Project description:Abstract: Objective: Adenomyosis is a clinical disorder defined by the presence of endometrial glands and stroma within the myometrium, the pathogenesis of which is poorly understood. We postulate that dysregulation of genes and pathways in eutopic endometrium may predispose to ectopic implantation. No study, to our knowledge, has examined the global transcriptome of isolated eutopic endometrium from women with clinically significant adenomyosis. Design: Laboratory-based study with full IRB approval and consents. Material and Methods: Endometrial sampling was performed on hysterectomy specimens (proliferative phase) from symptomatic women with pathologically-confirmed diffuse adenomyosis (n=3). Controls (n=5) were normo-ovulatory subjects without adenomyosis. All subjects were free from leiomyoma, endometriosis, and hormonal exposures. Isolated purified total RNA was subjected to microarray analysis using the Gene 1.0 ST Affymetrix platform. Data were analyzed with GeneSpring and Ingenuity Pathway analysis. Validation of several genes was undertaken by QRT-PCR. Results: Comparison of transcriptomes of proliferative endometrium from women with and without adenomyosis revealed 140 up-regulated and 884 down-regulated genes in samples from women with adenomyosis compared to controls. Highly differentially expressed genes include those involved in regulation of apoptopsis, steroid hormone responsiveness, and proteins involved in extracellular matrix remodeling, as well as microRNAs of unknown significance. Affected canonical pathways included eukaryotic initiation factor 2 signaling, oxidative phosphorylation, mitochondrial dysfunction, estrogen receptor signaling, and mTOR signaling. Conclusions: The eutopic endometrium in patients with adenomyosis has fundamental abnormalities that may predispose to invasion and survival beyond the myometrial interface. Key Words: adenomyosis, endometrium, microarray, microRNA, endometriosis, apoptosis, signaling. Abstract: Objective: Adenomyosis is a clinical disorder defined by the presence of endometrial glands and stroma within the myometrium, the pathogenesis of which is poorly understood. We postulate that dysregulation of genes and pathways in eutopic endometrium may predispose to ectopic implantation. No study, to our knowledge, has examined the global transcriptome of isolated eutopic endometrium from women with clinically significant adenomyosis. Design: Laboratory-based study with full IRB approval and consents. Material and Methods: Endometrial sampling was performed on hysterectomy specimens (proliferative phase) from symptomatic women with pathologically-confirmed diffuse adenomyosis (n=3). Controls (n=5) were normo-ovulatory subjects without adenomyosis. All subjects were free from leiomyoma, endometriosis, and hormonal exposures. Isolated purified total RNA was subjected to microarray analysis using the Gene 1.0 ST Affymetrix platform. Data were analyzed with GeneSpring and Ingenuity Pathway analysis. Validation of several genes was undertaken by QRT-PCR. Results: Comparison of transcriptomes of proliferative endometrium from women with and without adenomyosis revealed 140 up-regulated and 884 down-regulated genes in samples from women with adenomyosis compared to controls. Highly differentially expressed genes include those involved in regulation of apoptopsis, steroid hormone responsiveness, and proteins involved in extracellular matrix remodeling, as well as microRNAs of unknown significance. Affected canonical pathways included eukaryotic initiation factor 2 signaling, oxidative phosphorylation, mitochondrial dysfunction, estrogen receptor signaling, and mTOR signaling. Conclusions: The eutopic endometrium in patients with adenomyosis has fundamental abnormalities that may predispose to invasion and survival beyond the myometrial interface. Key Words: adenomyosis, endometrium, microarray, microRNA, endometriosis, apoptosis, signaling. A total of 8 samples were used and analyzed by disease state. Endometrial samples from hysterectomy specimens in proliferative phase of menstrual cycle from symptomatic women with pathologically-confirmed diffuse adenomyosis were compared with endometrial samples from normo-ovulatory healthy subjects with no endometrial or uterine pathology.
2016-03-03 | E-GEOD-78851 | biostudies-arrayexpress
Project description:Adenomyosis is an estrogen-dependent disease in which endometrial glands and stroma are pathologically demonstrated in the myometrium. Despite its prevalence and severity of symptoms, the precise etiology and physiopathology of adenomyosis is not well understood.Vitamin defciency increase in women with adenomyosis. Much less is known about the mechanism of their relationship. We found the retinol-binding protein receptor STRA6 upregulation in uterinespiral arteries from adenomyosis patients. The increased estrogen level promote the STRA6 expression, resulting the depressed Wnt/β-catenin signaling mediated by FASN/GSK-3β interaction. Overexpression of STRA6 induced epithelial to mesenchymal transition process. miR-1249-5p achieved its negative function by regulating the target gene through 3' UTR.The depletion of STRA6 in vivo alleviated the pathogenesis of adenomyosis. These results reveal a hitherto undesribed positive feedback loop between estrogen and STRA6 in adenomyosis pathogenesis. Components of vitamin A metabolism network have more complex activities than simply controlling or transferring VA compounds between different cells.
2023-09-06 | GSE242148 | GEO
Project description:Adenomyosis is an estrogen-dependent disease in which endometrial glands and stroma are pathologically demonstrated in the myometrium. Despite its prevalence and severity of symptoms, the precise etiology and physiopathology of adenomyosis is not well understood.Vitamin defciency increase in women with adenomyosis. Much less is known about the mechanism of their relationship. We found the retinol-binding protein receptor STRA6 upregulation in uterinespiral arteries from adenomyosis patients. The increased estrogen level promote the STRA6 expression, resulting the depressed Wnt/β-catenin signaling mediated by FASN/GSK-3β interaction. Overexpression of STRA6 induced epithelial to mesenchymal transition process. miR-1249-5p achieved its negative function by regulating the target gene through 3' UTR.The depletion of STRA6 in vivo alleviated the pathogenesis of adenomyosis. These results reveal a hitherto undesribed positive feedback loop between estrogen and STRA6 in adenomyosis pathogenesis. Components of vitamin A metabolism network have more complex activities than simply controlling or transferring VA compounds between different cells.
2023-09-06 | GSE242145 | GEO
Project description:Glaucoma is a progressive optic neuropathy that can lead to irreversible blindness. Its main risk factor is elevated intraocular pressure (IOP). The trabecular meshwork (TM) acts as a filter between the anterior chamber of the eye and the aqueous humor collecting ducts, and dysfunction of this meshwork is responsible for the increased IOP in primary open-angle glaucoma (POAG). Considering that the culture conditions of human TM cells (HTMC) influence gene expression, we used human TM explants (HTMEx), which most closely mimic physiological conditions, to study the transcriptome of HTMC. The transforming growth factor-beta 2 (TGF-β2) signaling pathway has been implicated in the pathophysiology of POAG. To better characterize the role of TGF-β2 in this pathophysiology, we used bulk RNA sequencing and immunohistological analyses to establish gene signatures of TGF-β2-exposed HTMEx and correlate them with morphological alterations. We identified differentially upregulated genes primarily involved in ECM regulation, as well as profibrotic TGF-β signaling pathways, confirmed using confocal microscopy to highlight changes in trabecular architecture, TGFβ2-induced F-actin rearrangements, and extracellular matrix (ECM) deposition. Enrichment analysis also revealed modulations of gene expression related to cytoskeletal organization, as well as activation of the bone morphogenic protein (BMP) and Wnt signaling pathways in response to TGF-β2.
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Project description:The epidermal growth factor receptor (EGFR) is overexpressed in approximately 90% of head and neck squamous cell carcinomas (HNSCC), and molecularly targeted therapy against the EGFR with the monoclonal antibody cetuximab modestly increases overall survival in head and neck cancer patients. We hypothesize that co-signaling through additional pathways limits the efficacy of cetuximab and EGFR-specific tyrosine kinase inhibitors (TKIs) in the clinical treatment of HNSCC. Analysis of gene expression changes in HNSCC cell lines treated 4 days with TKIs targeting EGFR and/or fibroblast growth factor receptors (FGFRs) identified transforming growth factor beta 2 (TGF-β2) induction in the three cell lines tested. Measurement of TGF-β2 mRNA validated this observation and extended it to additional cell lines. Moreover, TGF-β2 mRNA was increased in primary patient HNSCC xenografts treated for 4 weeks with cetuximab, demonstrating in vivo relevance of these findings. Functional genomics analyses with shRNA libraries identified TGF-β2 and TGF-β receptors (TGFβRs) as synthetic lethal genes in the context of TKI treatment. Further, direct RNAi-mediated silencing of TGF-β2 inhibited cell growth, both alone and in combination with TKIs. Also, a pharmacological TGFβRI inhibitor similarly inhibited basal growth and enhanced TKI efficacy. In summary, the studies support a TGF-β2-TGFβR pathway as a TKI-inducible growth pathway in HNSCC that limits efficacy of EGFR-specific inhibitors.
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Project description:The study objectives were to 1) determine mesenchymal stem cell (MSC) surface expression of major histocompatibility complex (MHC) class I and transcriptome-wide gene expression changes following IL-1β + TGF-β2 dual licensing and 2) evaluate if IL-1β + TGF-β2 dual licensed MSCs had greater ability to positively modulate tenocyte function compared to naïve MSCs.
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