Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Potential Onco-Suppressive Role of miR122 and miR144 in Uveal Melanoma through ADAM10 and C-Met Inhibition

ABSTRACT: Uveal melanoma (UM) is a rare tumor of the eye that leads to deadly metastases in about half of the patients. ADAM10 correlates with c-Met expression in UM and high levels of both molecules are related to the development of metastases. MiR122 and miR144 modulate ADAM10 and c-Met expression in di erent settings. We hypothesized a potential onco-suppressive role for miR122 and miR144 through modulation of ADAM10 and c-Met in UM. We analyzed the UM Cancer Genome Atlas data portal (TCGA) dataset, two other cohorts of primary tumors and five human UM cell lines for miR122 and miR144 expression by miR microarray, RT-qPCR, Western blotting, miR transfection and luciferase reporter assay. Our results indicate that miR122 and miR144 are expressed at low levels in the UM cell lines and in the TCGA UM dataset and were down-modulated in a cohort of seven UM samples, compared to normal choroid. Both miR122 and miR144 directly targeted ADAM10 and c-Met. Overexpression of miR122 and miR144 led to reduced expression of ADAM10 and c-Met in the UM cell lines and impaired cell proliferation, migration, cell cycle and shedding of c-Met ecto-domain. Our results show that miR122 and miR144 display an onco-suppressive role in UM through ADAM10 and c-Met modulation.

ORGANISM(S): Homo sapiens

PROVIDER: GSE163942 | GEO | 2020/12/29

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Potential Onco-Suppressive Role of miR122 and miR144 in Uveal Melanoma through ADAM10 and C-Met Inhibition

Project description:Potential Onco-Suppressive Role of miR122 and miR144 in Uveal Melanoma through ADAM10 and C-Met Inhibition

| PRJNA688296 | ENA

MET regulates expression of co-stimulatory and co-inhibitory molecules in tumor cells and contributes to suppression of immune cell function

Project description:MET-altered human cancer cell lines including Hs746T (MET-mutated/amplified), H596 (MET-mutated) and H1993 (MET-amplified) cells were used. In microarray analysis, MET suppression using MET inhibitor or siRNAs up-regulated variable co-stimulatory molecules, including 4-1BBL, OX40L and CD70, and down-regulated variable co-inhibitory molecules. Among co-inhibitory molecules, PD-L1 was one of the most markedly down-regulated genes by MET suppression, which was validated at the mRNA and total/surface protein levels in Hs746T and H1993 cells. Consistently, MET activation by HGF treatment increased PD-L1 expression in H596 cells. Co-culture of human peripheral blood mononuclear cells (PBMC) with Hs746T cells suppressed IFNg production from PBMC, which was restored by an MET inhibitor or PD-L1 blockade. A significant positive correlation between MET and PD-L1 expression was observed in The Cancer Genome Atlas (TCGA) analysis for variable cancer types and immunohistochemistry for lung cancer. MET overexpression in PD-L1-high tumor exhibited decreased expressions of T-cell effector molecules in TCGA analysis for lung cancer. In summary, MET overexpression/activation is related to immunosuppressive phenotype and is involved in immune escape of tumor by PD-L1 up-regulation. MET-targeted therapy combined with immunotherapy could be a potential therapeutic strategy in MET-dependent cancer.

2019-08-20 | GSE135976 | GEO

The immune suppressive tumor microenvironment affects efficacy of radio-immunotherapy in breast-to-brain metastasis

Project description:The tumor microenvironment in brain metastases is characterized by high myeloid cell content with immune-suppressive and cancer-permissive functions. Moreover, brain metastases induce the recruitment of lymphocytes. Despite their presence, T cell-directed therapies fail to elicit effective anti-tumor immune responses. Here we seek to evaluate the applicability of radio-immunotherapy to modulate tumor immunity and overcome inhibitory effects that diminish anti-cancer activity. Radiotherapy-induced immune modulation resulted in an increase in cytotoxic T cell numbers and prevented the induction of lymphocyte-mediated immune suppression. Radio-immunotherapy led to significantly improved tumor control with prolonged median survival in experimental breast-to-brain metastases. However, long-term efficacy was not observed. Recurrent brain metastases showed accumulation of blood-borne PD-L1+ myeloid cells after radio-immunotherapy indicating the establishment of an immune-suppressive environment to counteract re-activated T cell responses. This finding was further supported by transcriptional analyses indicating a crucial role for monocyte-derived macrophages in mediating immune-suppression and regulating T cell function. Therefore, selective targeting of immune suppressive functions of myeloid cells is expected to be critical for improved therapeutic efficacy of radio-immunotherapy in brain metastases.

2021-02-12 | GSE164049 | GEO

Expression data from Adam10 knock out mice and wild type

Project description:Adam10, a cell surface protease, cleaving many proteins including TNF-alpha and E-cadherin. Here we investigate the genome wide effects of Adam10 knock out on the transcriptome. Commercial microarrays (Affymetrix Mouse Gene ST 1.0) were used to generate genome wide mRNA profiles. Mouse tissue samples from n=4 wiltype skin and n=4 Adam10 knockout skin were used in the study.

2011-01-06 | E-GEOD-25480 | biostudies-arrayexpress

Tetraspanin Tspan15 is an essential subunit of an ADAM10 scissor complex

Project description:A disintegrin and metalloprotease 10 (ADAM10) is essential for embryonic development and impacts on diseases such as cancer, Alzheimer’s and inflammatory diseases. ADAM10 is a ‘molecular scissor’ that proteolytically cleaves the extracellular region from over 100 substrates, including Notch, amyloid precursor protein, cadherins, growth factors and chemokines. ADAM10 was recently proposed to function as six distinct scissors with different substrates, depending on its association with one of six regulatory tetraspanins, termed TspanC8s. However, it remains unclear whether ADAM10 function is critically dependent on a TspanC8 partner. To address this, we generated the first monoclonal antibodies to Tspan15 as a model TspanC8. These were used to show that ADAM10 is the principal Tspan15-interacting protein, that Tspan15 expression requires ADAM10 in cell lines and primary cells, and that a synthetic ADAM10/Tspan15 fusion protein is a functional scissor. Together these findings suggest that ADAM10 exists as an ADAM10/TspanC8 scissor complex.

2021-08-24 | PXD016508 | Pride

1,4-dihydroxy Quininib Activates Ferroptosis Pathways in Metastatic Uveal Melanoma and Reveals a Novel Prognostic Biomarker Signature

Project description:Uveal melanoma (UM) is an ocular cancer, with propensity for lethal liver metastases. When metastatic UM (MUM) occurs, as few as 8% of patients survive beyond two years. Efficacious treatments for MUM are urgently needed. 1,4-dihydroxy quininib, a cysteinyl leukotriene receptor 1 (CysLT1) antagonist, alters UM cancer hallmarks in vitro, ex vivo and in vivo. Here, we investigated the 1,4-dihydroxy quininib mechanism of action and its translational potential in MUM.

2024-06-16 | PXD046822 | Pride

Molecular profiling of driver events in metastatic uveal melanoma

Project description:Uveal melanoma (UM) is a rare form of melanoma with a genetics and immunology that is different from skin melanoma. Previous studies have identified genetic driver events of early stage disease when the tumor is confined to the eye. In this study, we have characterized genomic events in UM metastases using whole-genome and RNA sequencing from thirty-two and twenty-eight patients, respectively, and profiled individual tumor infiltrating lymphocytes in a number of the metastases. We find that 91% of the patients have metastases carrying inactivating events in the tumor suppressor BAP1 and this coincided with somatic alterations in GNAQ, GNA11, CYSLTR2, PLCB4, SF3B1 and/or CDKN2A. Mutational signature analysis revealed a rare subset of tumors with prominent signs of UV damage, associated with outlier mutational burden. We study copy number variations (CNV) and find overrepresented events, some of which were not altered in matched primary eye tumors. A focused siRNA screen identified functionally significant genes of some of the segments recurrently gained. We reintroduced a functional copy of BAP1 into a patient-derived BAP1 deficient tumor cell line and found broad transcriptomic changes of genes associated with subtype distinction and prognosis in primary UM. Lastly, our analysis of the immune microenvironments of metastases revealed a presence of tumor-reactive T cells. However, a large fraction expressed the immune checkpoint receptors such as TIM-3, TIGIT and LAG3. These results provide an updated view of genomic events represented in metastatic UM and immune interactions in advanced lesions.

2020-03-18 | PXD017743 | Pride

Genome wide expression analysis of FABP4 modulation in urothelial cancer cell UM-UC14 and UM-UC9

Project description:Analysis of gene expression profiling in FABP4 modulation UM-UC14 and Um-UC9 cells. The overall objective was to identify genes regulated by PPARγ signaling pathway in particular FABP4

2014-02-17 | GSE47993 | GEO

Lenses expression profile of DBL oncogene transgenic mice

Project description:The Dbl family of proteins represents a large group of proto-oncogenes involved in cell growth regulation. Alterations of the normal function of these proteins lead to pathological processes such as developmental disorders and neoplastic transformation. We have generated transgenic mice introducing the onco-Dbl cDNA sequences linked to the metallothionein promoter into the germ line of FVB mice and found that onco-Dbl expression affected proliferation, migration and differentiation of lens epithelial cells. We used high density oligonucleotide microarray to define the transcriptional profile induced by Dbl in the lenses of transgenic mice and observed modulation of genes encoding proteins promoting epithelial-mesenchymal transition (EMT). Moreover, genes encoding proteins involved in the positive regulation of apoptosis were markedly down regulated while anti-apoptotic genes were strongly up-regulated. Finally, several genes encoding proteins involved in the process of angiogenesis were up-regulated. These observations were validated by histological and immunohistochemical examination of the transgenic lenses, where vascularization can be readily observed. Thus, onco-Dbl expression in mouse lenses induces disruption of the lens architecture, epithelial cell proliferation, EMT, evasion from cell death, and aberrant angiogenesis. Whole lenses were removed from 2, 14, and 42 day old Dbl transgenic and wild type mice. 4 to 8 individual lenses were pooled . Three independent pools from each time and condition were used as replicates.

2009-06-01 | E-GEOD-15694 | biostudies-arrayexpress

Project description:UM metastases pre and early during PKC inhibitor-based therapy

| PRJNA1125170 | ENA