Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

MiRNA profiling in MMP-8 overexpressing MDA-MB-231 cells

ABSTRACT: Matrix metalloproteinases (MMPs) have been traditionally implicated in cancer progression because of their ability to degrade the extracellular matrix. However, some members of the MMP family have recently been identified as proteases with antitumor properties. Thus, it has been described that collagenase-2 (MMP-8) has a protective role in tumor and metastasis progression, but the molecular mechanisms underlying these effects are unknown. We show herein that Mmp8 expression causes a decrease in miR-21 levels that in turn leads to a reduction in tumor growth and lung metastasis formation by MDA-MB-231 (4175) breast cancer cells. By using both in vitro and in vivo models, we demonstrate that the mechanism responsible for these MMP-8 beneficial effects involves cleavage of decorin by MMP-8 and a subsequent reduction of transforming growth factor ? (TGF-?) signaling that controls miR-21 levels. In addition, miR-21 downregulation induced by MMP-8 increases the levels of tumor suppressors such as programmed cell death 4, which may also contribute to the decrease in tumor formation and metastasis of breast cancer cells overexpressing this metalloproteinase. These findings reveal a new signaling pathway for cancer regulation controlled by MMP-8, and contribute to clarify the molecular mechanisms by which tumor-defying proteases may exert their protective function in cancer and metastasis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE124432 | GEO | 2019/01/27

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

MiR-21 Promotes Glioma Invasion by Targeting MMP Regulators.

Project description:Substantial data indicate that microRNA-21 (miR-21) is significantly elevated in glioblastoma (GBM) and in many other tumors of various origins. This miRNA has been implicated in various aspects of carcinogenesis, including cellular proliferation, apoptosis and migration. We demonstrate that miR-21 regulates multiple genes associated with glioma cell apoptosis, migration, and invasiveness, including RECK and TIMP3, suppressors of malignancy and inhibitors of matrix metalloproteinases (MMPs). Specific inhibition of miR-21 with antisense olgonucleotides leads to elevated levels of RECK and TIMP3 and therefore reduces MMP activities in vitro and in a human model of glioma in nude mice. Moreover, down-regulation of miR-21 in glioma cells leads to decrease of their migratory and invasion abilities. Our data suggest that miR-21 contributes to the glioma malignancy by down-regulation of MMP inhibitors that leads to activation of MMPs thus promoting invasiveness of cancer cells. Our results also indicate that inhibition of a single oncomir like miR-21 with specific antisense molecules can provide a novel therapeutic approach for “physiological” modulation of multiple proteins whose expression is de-regulated in cancer.

2008-07-12 | GSE11778 | GEO

Genome-wide profiles of multiple histone modifications in MDA-MB-231 and LM2-4175 cell lines

Project description:LM2-4175 cell line was originally selected from MDA-MB-231,but has more aggressive characteristics in invasion, migration and metastasis. In addition, LM2 cell line specifically metastasizes to lung. To understand the regulatory mechanisms of lung metastasis in breast cancer, we analyzed the chromatin structure of MDA-MB-231 and LM2-4175 cell lines.

2019-07-31 | GSE124379 | GEO

Next generation sequencing analysis of transcriptomes in MDA-MB-231 and LM2-4175 cell lines

Project description:LM2-4175 cell line was originally selected from MDA-MB-231,but has more aggressive characteristics in invasion, migration and metastasis. In addition, LM2 cell line specifically metastasizes to lung. To understand the melecular mechanisms of lung metastasis in breast cancer,we analyzed the RNA-seq data of MDA-MB-231 and LM2-4175 cell lines.

2019-07-31 | GSE124380 | GEO

Drosha/Dicer/miR-7/TGF-β2 axis Sustained Acidic Microenvironment-induced Lung Metastasis

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

The microRNAs with potential in predicting lung metastasis of triple negative breast cancer

Project description:To identify lung metastasis associated microRNAs in triple negative breast cancer (TNBC), we have employed the commercially available Agilent Human miRNA V19.0 Microarray (Platform GPL19730) as a discovery platform. In comparison with LM-Normal, 11 microRNAs significantly altered in both LM-Met and LM-Tumor, and then three of them (hsa-miR-21-3p, hsa-miR-21-5p and hsa-miR-211-3p) were excluded, which were also up-regulated in RF-Tumor. Consequently, eight deregulated microRNAs were identified to be putatively involved in process of lung metastasis, especially miR-629-3p, which was most up-regulated in both LM-Met and LM-Tumor. To validate the microarray data, we utilized qRT-PCR to assess expression levels of the eight miRNAs in the same samples.

2016-04-08 | GSE80038 | GEO

miR-21 is critical in stress response and facilitates breast cancer development and metastasis [miRNA array]

Project description:miR-21 is upregulated in advanced tumor stages, distal metastasis, and poor survival and in response to cytotoxic stress, but is also known to confer resistance to radiation and chemotherapy. We discovered that global ablation of miR-21 significantly decreased tumorigenesis and metastatic spread of breast cancer, while sensitizing breast carcinomas to cytotoxic agents by evoking Fas/FasL-dependent apoptosis. Targeting miR-21 may represent a novel and efficacious therapeutic modality either alone or in combination with standard oncologic treatments.

2022-02-01 | GSE145344 | GEO

A mechanistic study on the metastasis inducing function of FUS-CHOP fusion protein in liposarcoma

Project description:Identification of differential gene regulation pattern in human liposarcoma The FUS-CHOP fusion protein has been found to be instrumental for specific oncogenic processes in liposarcoma, but its ability to induce metastasis and the underlying mechanisms by which this can be achieved remain unknown. In order to dissect its functional role in this context, we stably overexpressed this protein in SW872 liposarcoma and HT1080 fibrosarcoma cell lines, and were able to demonstrate that forced expression of FUS-CHOP significantly increases migration and invasion, as well as enhance lung and liver metastasis in the in vivo chicken chorioallantoic membrane (CAM) model, that is proliferation independent. Additionally, FUS-CHOP enhances the expression of matrix-metalloproteinases -2 and -9, and transactivates their promoters in vitro. Mutational analysis showed that C/EBP-β- (-769/-755), NF-κB (-525/-516) and CREB/AP-1 (-218/-207) sites were important for MMP-2, and NF-κB (-604/-598), AP-1 (-539/-532) and AP-1 (-81/-72) for MMP-9 transactivation. Moreover, a direct in vivo interaction of FUS-CHOP was observed in case of the MMP-2 promoter within region (-769/-207). siRNA data revealed that MMP-2 expression is essential in the FUS-CHOP induced metastatic phenotype. MMP-2-mRNA and protein expression correlated significantly with FUS-CHOP positivity in 31 resected patient liposarcoma tissues. We have for the first time provided substantial evidence for the FUS-CHOP oncoprotein as an inducer of metastasis that is due to the transcriptional induction of specific tumor-associated proteases. Insights gained from this study not only support a deeper understanding of the mechanistic properties of FUS-CHOP, but also open up new avenues for targeted therapy. 3 liposarcoma tumor samples, 3 corresponding normal samples, one sample replicated

2013-09-20 | E-GEOD-51049 | biostudies-arrayexpress

Protein expression profile of miR-33b overexpressing ES-2 cells upon OCM treatment

Project description:Omentum conditioned medium (OCM) is known to enhance ovarian cancer oncogenesis. In this study, miR-33b exerts tumor suppressive effects on ovarian cancer cells in response to omentum conditioned medium (OCM) treatment. To identify the molecular mechanism and main biological pathways involved in the tumor inhibiting activity by miR-33b in the ovarian cancer metastasis. To achieve this, miR-33b was stably overexpressed in ovarian cancer cell line ES-2, and the protein expression profile of miR-33b overexpressing ES-2 cells upon OCM treatment was determined.

2022-02-17 | PXD026901 | Pride

miR-21 plays a dual role in tumor formation and cytotoxic response in breast tumors

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

Colorectal Cancer-derived Small Extracellular Vesicles Create an Inflammatory Pre-metastatic Niche through Macrophage Polarization in Liver Metastasis

Project description:Colon and liver have an inseparable relationship since embryological development. More than half of colorectal cancer patients developed liver metastases accompanied with poor prognosis. Recent evidence suggests that distant metastatic organs are “educated” by primary tumor-derived extracellular vesicles. Here we found that the liver-specific pro-metastatic effect of colorectal cancer (CRC)-derived small extracellular vesicles (sEVs). In vivo experiments showed that the injected fluorescence-labeled CRC-derived sEVs were accumulated and taken up by macrophages in the mouse liver. MicroRNA sequencing revealed the highest expression of microRNA (miR)-21-5p in CRC-derived sEVs. In vitro co-culture experiments showed that the sEVs polarized macrophages toward an interleukin-6(IL-6)-secreting type of macrophages. Further mouse experiments and microarray studies indicated that the CRC-sEVs increased macrophage invasion and induced an inflammatory microenvironment in the liver, which promoted liver metastasis of orthotropic- transplanted CRC cells. Most importantly, the TCGA data analysis and clinical sample examinations demonstrated that miR-21-5p expressions were sharply raised in the CRC tissues. We apply Tethered Cationic Lipoplex Nanoparticles (tCLN) technology in detecting CRC patients’ sEVs miR-21 in plasma and found strong correlation between sEVs-miR-21 and CRC liver metastasis. The serum IL-6 level was much higher in CRC patients with liver metastasis, and the liver metastasis relevance of MiR-21, macrophages, and IL-6 in CRC patients. Thus, we propose the role of CRC-derived sEVs in the formation of an inflammatory pre-metastatic niche in liver for CRC metastasis through macrophage polarization via a miR-21/TLRs pro-inflammation pathway.

2019-07-01 | GSE100435 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data