MiR-21 is critical in stress response and facilitates breast cancer development and metastasis [miRNA array]
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE145344 | GEO | 2022/02/01
REPOSITORIES: GEO
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Project description:Breast cancer (BrCa) relies on specific microRNAs to drive disease progression. Oncogenic miR-21 is upregulated in many cancers including BrCa and is associated with poor survival and treatment resistance. We sought to determine the role of miR-21 in BrCa tumor initiation, progression and treatment response. In a triple-negative BrCA model, radiation exposure increased miR-21 in both primary tumor and metastases. In vitro, miR-21 knockdown decreased survival in all BrCa subtypes in presence of radiation. The role of miR-21 to BrCa initiation was evaluated by implanting wild-type miR-21 BrCa cells into genetically-engineered mouse models where miR-21 was intact, heterozygous or globally ablated. Tumors were unable to grow in mammary fat pads of miR-21-/- mice, grew in ~50% of miR-21+/- and 100% in miR-21+/+ mice. The contribution of miR-21 in progression and metastases was tested by crossing miR-21-/- mice with mice that spontaneously develop BrCa. Global ablation of miR-21 significantly decreased tumorigenesis and metastases of BrCa while sensitizing tumors to radio- and chemotherapeutic agents by a Fas/FasL-dependent apoptosis. Therefore, targeting miR-21 alone or in combination with various radio or cytotoxic therapies may represent novel and efficacious therapeutic modalities for the future treatment of BrCa patients. We used microarray to identify gene expression associated with miR-21 function in breast development and metastasis.
2021-03-10 | GSE144773 | GEO
Project description:Fas ligand (FasL)/TNFSF6, a member of the tumor necrosis factor (TNF) superfamily, can promote apoptosis in activated primary B cells, T cells, dendritic cells, and synovial fibroblasts through Fas and is involved in the pathogenesis of autoimmune diseases including rheumatoid arthritis (RA). Meanwhile, decoy receptor 3 (DcR3) competitively binds soluble FasL in addition to TL1A and LIGHT and inhibits the signaling of FasL via Fas. Therefore, FasL-DcR3/Fas signaling may be involved in the pathogenesis of RA. We hypothesized that FasL regulates the gene expression in RA-FLS. We used to search for genes in which expression in RA-FLS is regulated by FasL.
2020-06-30 | GSE153378 | GEO
Project description:A fine regulation of epithelia cell death is required to maintain tissue integrity and homeostasis. At a cellular level, this life and death decision is controlled by environmental stimuli including death receptors activation. Here, we show that establishment of cell polarity and AJ formation control the pro-apoptotic signaling emanating from the death receptor Fas. We demonstrate that in colon epithelia Fas concentrates at cell-cell junctions together with the E-cadherin, which protects cells from FasL-induced cell death. The Fas-cadherin association requires the C terminal PDZ binding site of Fas and, using a proteomic approach, we showed that this domain allows the association with the polarity molecule Dlg1. We proved that the interaction of Fas with this scaffold molecule participate to this cell death protection. Therefore inhibition of FasL-induced cell death by Fas-cadherin-Dlg1 complex is a double-edged sword mechanism that helps to maintain epithelial homeostasis by (i) protecting normal polarized epithelia from apoptosis (ii) promoting the elimination of compromised non-polarized cells.
2018-09-20 | PXD009659 | Pride
Project description:Webb2002 - Fas/FasL mediated tumor T-cell interaction
This deterministic model of
immunological surveillance involving tumour cell–T-lymphocyte
interaction, cell surface expression of Fas/FasL, and their
secreted soluble forms.
This model is described in the article:
Cells behaving badly: a
theoretical model for the Fas/FasL system in tumour
immunology.
Webb SD, Sherratt JA, Fish RG.
Math Biosci 2002 Sep-Oct; 179(2):
113-129
Abstract:
One proposed mechanism of tumour escape from immune
surveillance is tumour up-regulation of the cell surface ligand
FasL, which can lead to apoptosis of Fas receptor (Fas)
positive lymphocytes. Based upon this 'counterattack', we have
developed a mathematical model involving tumour cell-lymphocyte
interaction, cell surface expression of Fas/FasL, and their
secreted soluble forms. The model predicts that (a) the
production of soluble forms of Fas and FasL will lead to the
down-regulation of the immune response; (b) matrix
metalloproteinase (MMP) inactivation should lead to increased
membrane FasL and result in a higher rate of Fas-mediated
apoptosis for lymphocytes than for tumour cells. Recent studies
on cancer patients lend support for these predictions. The
clinical implications are two-fold. Firstly, the use of broad
spectrum MMP inhibitors as anti-angiogenic agents may be
compromised by their adverse effect on tumour FasL
up-regulation. Also, Fas/FasL interactions may have an impact
on the outcome of numerous ongoing immunotherapeutic trials
since the final common pathway of all these approaches is the
transduction of death signals within the tumour cell.
This model is hosted on
BioModels Database
and identified by:
BIOMD0000000661.
To cite BioModels Database, please use:
Chelliah V et al. BioModels: ten-year
anniversary. Nucl. Acids Res. 2015, 43(Database
issue):D542-8.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
CC0
Public Domain Dedication for more information.
2024-09-02 | BIOMD0000000661 | BioModels
Project description:Ocular immune privilege (IP) limits immune surveillance of intraocular tumors as certain immunogenic tumor cell lines (P815, E.G7-OVA) that are rejected when transplanted in the skin grow progressively when placed in the anterior chamber (a.c.) of the eye. As splenectomy (SPLNX) is known to terminate ocular IP, we characterized immune mechanisms responsible for spontaneous rejection of intraocular tumors in SPLNX mice as a first step toward identifying how to restore tumoricidal activity within the eye. Microarray data showed a 3-fold increase in interferon (IFN)-γ and a 2.7-fold increase in Fas ligand (FasL). There was a robust increase in transcripts (127 of 408 surveyed) from interferon (IFN)-stimulated genes and a marked decrease (in 40 of 192 surveyed) in the expression of cell-cycle-associated genes. Non-microarray data confirmed that IFNγ, FasL and CD8+ T cells but not perforin or TNFα were required for elimination of intraocular E.G7-OVA tumors that culminated in destruction of the eye (ocular phthsis). IFNγ and FasL did not target tumor cells directly as the majority of SPLNX IFNγR1-/- mice and Fas-defective lpr mice failed to eliminate ocular E.G7-OVA tumors that expressed Fas and IFNγR1. Bone marrow chimeras showed that immune cell expression of IFNγR1 and Fas was critical and that SPLNX increased the frequency of activated macrophages within ocular tumors in an IFNγ- and Fas/FasL-dependent manner. Rejection of intraocular tumors was associated with increased ocular mRNA expression of several inflammatory genes including FasL, NOS2, CXCL2 and T-bet. Our data support a model in which IFNγ- and Fas/FasL-dependent activation of intratumoral macrophage by CD8+ T cells promotes severe intraocular inflammation that indirectly eliminates intraocular tumors by inducing phthisis. The immunosuppressive mechanisms which maintain ocular IP likely interfere with the interaction between CD8+ T cells and macrophage to limit immunosurveillance of intraocular tumors. C57BL/6 mice that were splenectomized (Tumor_splnx) or were not surgically manipulated (Tumor_intact) were challenged with 10^4 luciferase-expressing E.G7-OVA cells injected into the anterior chamber of the eye. Fifteen days later, the animals were euthanized and tumor-bearing eyes were removed.
2014-07-01 | E-GEOD-57101 | biostudies-arrayexpress
Project description:Ocular immune privilege (IP) limits immune surveillance of intraocular tumors as certain immunogenic tumor cell lines (P815, E.G7-OVA) that are rejected when transplanted in the skin grow progressively when placed in the anterior chamber (a.c.) of the eye. As splenectomy (SPLNX) is known to terminate ocular IP, we characterized immune mechanisms responsible for spontaneous rejection of intraocular tumors in SPLNX mice as a first step toward identifying how to restore tumoricidal activity within the eye. Microarray data showed a 3-fold increase in interferon (IFN)-γ and a 2.7-fold increase in Fas ligand (FasL). There was a robust increase in transcripts (127 of 408 surveyed) from interferon (IFN)-stimulated genes and a marked decrease (in 40 of 192 surveyed) in the expression of cell-cycle-associated genes. Non-microarray data confirmed that IFNγ, FasL and CD8+ T cells but not perforin or TNFα were required for elimination of intraocular E.G7-OVA tumors that culminated in destruction of the eye (ocular phthsis). IFNγ and FasL did not target tumor cells directly as the majority of SPLNX IFNγR1-/- mice and Fas-defective lpr mice failed to eliminate ocular E.G7-OVA tumors that expressed Fas and IFNγR1. Bone marrow chimeras showed that immune cell expression of IFNγR1 and Fas was critical and that SPLNX increased the frequency of activated macrophages within ocular tumors in an IFNγ- and Fas/FasL-dependent manner. Rejection of intraocular tumors was associated with increased ocular mRNA expression of several inflammatory genes including FasL, NOS2, CXCL2 and T-bet. Our data support a model in which IFNγ- and Fas/FasL-dependent activation of intratumoral macrophage by CD8+ T cells promotes severe intraocular inflammation that indirectly eliminates intraocular tumors by inducing phthisis. The immunosuppressive mechanisms which maintain ocular IP likely interfere with the interaction between CD8+ T cells and macrophage to limit immunosurveillance of intraocular tumors.
2014-07-01 | GSE57101 | GEO
Project description:Interventions: Normal mucosa:Normal mucosa;Adenoma:Adenoma;Early colorectal cancer:Early colorectal cancer;Advanced cancer:Advanced cancer;Advanced cancer:Advanced cancer;Paracancer tissues :Paracancer tissues
Primary outcome(s): Gender;Age;Location;HLA-A;Fas;CCR5;FasL;HLA-E
Study Design: Cohort study
| 2669919 | ecrin-mdr-crc
Project description:miR-21 is overexpressed in breast cancer cells. Knock-down of miR-21 cause apoptosis and decreased cell proliferation. To identify miR-21 regulated cancer-pathways in MCF-7 cells, we knocked-down miR-21 and performed microarray.
2014-03-01 | GSE52674 | GEO
Project description:miR-21 plays a dual role in tumor formation and cytotoxic response in breast tumors
| PRJNA604816 | ENA
Project description:Some unicellular organisms exhibit collective decision-making through intercellular communication once a quorum of members sense an environmental stress. Whether T cells at different states of differentiation may also synchronize their behavior on a population basis through direct interactions remains unclear. We report that memory CD8+ T cells (TMem) directly interact with naive T cells (TN) during priming, affecting the phenotypic, functional, transcriptional and metabolic differentiation of TN-derived progeny. This previously unrecognized, contact and concentration-dependent interaction between naive (TN) and memory CD8+ T cells (TMem) directly enhanced TN effector differentiation through non-apoptotic Fas signaling resulting in downstream Akt pathway activation. TN primed with TMem exhibited significantly impaired persistence and antitumor activity compared with TN primed alone. Disruption of FasL-Fas signaling in TN cells limited differentiation and enhanced anti-tumor immunity while provision of exogenous FasL in the absence of TMem impaired anti-tumor immunity by augmenting TN differentiation. These findings reveal that the full therapeutic potential of TN-derived cells for adoptive immunotherapy requires physical separation from TMem prior to priming or antagonism of Fas-signaling.
2015-03-01 | GSE56344 | GEO