Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The microRNAs miR-373 and miR-520c promote tumor migration, invasion and metastasis

ABSTRACT: MicroRNAs (miRNAs) are single-stranded noncoding RNAs that play important roles in many biological processes. Although the oncogenic and tumor suppressive functions of several miRNAs have been characterized, the role of miRNAs in mediating tumor metastasis was only recently addressed and still remain largely unexplored. To identify potential metastasis-promoting miRNAs, we set up a genetic screen using a non-metastatic human breast tumor cell line that was transduced with a miRNA expression library and subjected to a trans-well migration assay. We found human miR-373 and 520c to stimulate cancer cell migration as well as tumor cell invasion in vitro and in vivo, and that certain cancer cell lines depend on endogenous miR-373 activity to migrate efficiently. Mechanistically, the migration phenotype of miR-373 and miR-520c can be explained by their suppression of CD44 expression. Finally, we found significant up-regulation of miR-373 expression in clinical breast cancer primary and metastasis samples that inversely correlated with CD44 expression. Taken together, our study indicates that miRNAs are involved in tumor migration and invasion and implicates miR-373 and conceivably miR-520c as metastasis-promoting miRNAs. Keywords: human breast cancer cell MCF7 vs MCF7 expressing miR-373 vs MCF7 expressing miR-520c

ORGANISM(S): Homo sapiens

PROVIDER: GSE9742 | GEO | 2007/12/04

SECONDARY ACCESSION(S): PRJNA103659

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Suppression of miRNA-708 by polycomb group promotes metastases by calcium-induced cell migration

Project description:The progression of cancer to metastatic disease is a major cause of death. We identified miR-708 being transcriptionally repressed by polycomb repressor complex (PRC2)-induced H3-K27 trimethylation in metastatic breast cancer. miR-708 targets the endoplasmic reticulum protein neuronatin (Nnat) to decrease intracellular calcium (Ca2+) level, resulting in reduction of activation of ERK and FAK, decreased cell migration, and impaired metastases. Functional complementation experiments with Nnat-3’UTR mutant, which is refractory to suppression by miR-708, rescued cell migration and metastasis defects. In breast cancer patients, miR-708 expression was decreased in lymph node and distal metastases, suggesting a metastasis-suppressive role. Our findings uncover a mechanistic role for miR-708 in metastasis and provide a rationale for developing miR-708 as a therapeutic agent against metastatic breast cancer. Sequencing miRNAs from Human breast cancer cells: MCF10A, MCF7, MDA-MB-231, MDA-MB-LM2

2013-11-15 | E-GEOD-42313 | biostudies-arrayexpress

LSD1 inhibits the invasion and migration of breast cancer through exosomes

Project description:Metastasis accounts for almost 90% of breast cancer-related fatalities, making it frequent malignancy and the main reason of tumor mortality globally among women. A key player in breast cancer is the histone demethylase lysine-specific demethylase 1 (LSD1). We used LSD1 knockdown MCF7 and T47D cell exosomes to treat breast cancer cells for greatly increasing the invasion and migration of breast cancer cells for evaluating the impact of LSD1 on breast cancer invasion and migration. miR-1290 expression was downregulated in LSD1 knockdown MCF7 exosomes. Furthermore, miR-1290 could control NAT1 expression by looking through the database of miR-1290 target genes. These data provide fresh insights into the biology of breast cancer therapy by demonstrating how the epigenetic factor LSD1 stimulates the breast cancer cells’ invasion and migration via controlling exosomal miRNA.

2024-07-31 | GSE266982 | GEO

c-Src functionality controls self-renewal, tumorigenicity and glucose metabolism in breast cancer stem cells

Project description:Deregulation of Src kinases is associated with cancer. We previously showed that SrcDN conditional expression in MCF7 cells diminished tumorigenesis and causes tumor regression in mice. However, it remained unclear whether SrcDN affected breast cancer stem cell functionality or it reduced tumor mass. Here, we address this question by isolating an enriched population of BCSCs (ESA+-CD44+-CD24-) and the tumor-differentiated cells (ESA+-CD44+-CD24+) from MCF7-Tet-On-SrcDN. ESA+-CD44+-CD24- grew in suspension forming mammospheres, and producing tumors in nude mice, while ESA+-CD44+-CD24+ were poorly/non-tumorigenic. Doxycycline-induction of SrcDN inhibited BCSC tumorigenesis, selfrenewal, and stem-cell markers expression. SrcDN significantly inhibited SFE, and stem-cell markers expression in triple-negative breast cancer (TNBC) MDA-MB-231 and SUM159PT cells. Inducible depletion of c-Src caused similar effects in MDA-MB-231 cells. In MCF7-Tet-On-SrcDN derived mammospheres SrcDN-induction inhibited expression, and activity of hexokinase, pyruvate kinase and lactate dehydrogenase, resulting in diminished glucose consumption and lactate production, which restricted Warburg effect. Thus, c-Src functionality is important for breast cancer stem cell maintenance and renewal, tumorigenicity, and stem cell transcription factor expression, effects linked to glucose metabolism reduction.

2020-07-23 | PXD017789 | Pride

microRNA suppresses prostate cancer stem cells and metastasis by inhibiting a cohort of pro-metastasis targets including CD44, Rho GTPases and EZH2

Project description:microRNA plays important roles in tumor initiation and progression. Here we showed that, one of the miR-200 family member, miR-141 is drastically under-expressed in several prostate cancer stem cell populations in both xenograft and primary patient samples. Enforced expression of miR-141 in CD44+ PCa cells suppressed tumor initation and metastasis. Cancer stem cell related properties including clonal and sphere formation ability as well as migration and invasion abilites were blocked by miR-141. Moreover, under-expression of miR-141 in prostate cancer stem cells is important in maintaining a partial mesenchymal status. Whole genome sequencing revealed novel pathways that are regulated by miR-141 including Rho GTPase signaling pathway. Stem cell related molecules including CD44 and EZH2 are also validated as direct targets of miR-141 mediating the tumor and metastasis suppressive function. Altogether, these data suggests that on e signal miRNA, miR-141 could utilize multiple mechanisms to obstruct tumor progression and metstasiss. Total transcriptome profiles of prostate cancer cells Du145 and LAPC9 transfected with 30nM miR-141 mimicking oligonucleotides or negative control (NC) oligonucleotides were generated by deep sequencing, in duplicates, using Illumina HiSeq 2000.

2016-08-15 | E-GEOD-71756 | biostudies-arrayexpress

Homo sapiens

Project description:The microRNAs miR-373 and miR-520c promote tumor migration, invasion and metastasis

| PRJNA103659 | ENA

The miRNA miR-139-5p is a regulator of metastatic pathways in breast cancer.

Project description:Whole transcriptome Identification of direct targets of miR-139-5p using biotinylated pull-downs found that this miRNA has roles in breast cancer invasion and migration. MCF7 cells were transfected with biotinylated miR-139-5p. The miRNAs and target mRNA were pulled down with streptavidin and compared to the input control.

2013-12-01 | E-GEOD-40411 | biostudies-arrayexpress

Let-7 miRNAs and isoforms of miR-203a involve in regulation of colon cancer metastasis by receptor CD44

Project description:Metastasis formation represents a formidable challenge to oncologists due to limits the survival of colorectal cancer (CRC) patients. Recently we demonstrated that CD44 promotes spontaneous distant metastasis in a CRC xenograft model through primary tumor-related effects. The depletion of CD44 was associated with reduction in hypoxia, EMT, and improved mitochondrial metabolism. Together these effects limit the metastatic propensity of the tested CRC xenograft tumors. In this study we address to molecular mechanisms of how CD44 knockdown (kd) can result in such substantial changes of tumor properties. Base on the data of miRNA-Seq in combination of bioinformatic analysis the role of miRNA expression changes in the metastasis prevention by CD44 kd was investigated. Among all differentially expressed miRNAs three upregulated miRNAs of Let-7 family (hsa-let-7a-5p, hsa-let-7b-5p, and hsa-let-7c-5p) and two upregulated isoforms of miR-203a (canonical has-miR-203a-3p and its +1 5'-isoform) were revealed as potentially involved in regulation of CD44-mediated metastasis. The results of gene set analysis of differentially expressed mRNA-targets of these miRNAs and analysis of key regulators involved in the determined changes of both mRNA and miRNA expression profiles suggests CD44-STAT3-Let-7 miRNAs axis as one of the most relevant in regulation of colon cancer metastasis by CD44.

2024-12-19 | GSE284708 | GEO

Identification and Validation of Genes with Expression Patterns Inverse to Multiple Metastasis Suppressor Genes in Breast Cancer Cell Lines

Project description:Metastasis suppressor genes (MSGs) have contributed to an understanding of regulatory pathways unique to the lethal metastatic process. When re-expressed in experimental models, MSGs block cancer spread to, and colonization of distant sites without affecting primary tumor formation. On a single MSG basis, genes have been identified with expression patterns inverse to a MSG, and found to encode functional, druggable signaling pathways. We now hypothesize that common signaling pathways mediate the effects of many MSGs. By gene expression profiling of human MCF7 breast carcinoma cells expressing a scrambled siRNA or siRNAs to each of 19 validated MSGs (NME1, BRMS1, CD82, CDH1, CDH2, CDH11, CASP8, MAP2K4, MAP2K6, MAP2K7, MAPK14, GSN, ARHGDIB, AKAP12, DRG1, CD44, PEBP1, RRM1, KISS1), we identified genes whose expression was significantly opposite to at least five MSGs. We used microarrays to evaluate the modification in gene expression profile after donregulation of multiple metastasis suppressors (NME1, BRMS1, CD82, CDH1, CDH2, CDH11, CASP8, MAP2K4, MAP2K6, MAP2K7, MAPK14, GSN, ARHGDIB, AKAP12, DRG1, CD44, PEBP1, RRM1, KISS1) in the breast cancer cell line, MCF7. MCF7 cell line was transfected with siRNA targeting each of 19 metastasis suppressors (NME1, BRMS1, CD82, CDH1, CDH2, CDH11, CASP8, MAP2K4, MAP2K6, MAP2K7, MAPK14, GSN, ARHGDIB, AKAP12, DRG1, CD44, PEBP1, RRM1, KISS1). Two siRNA sequences (siRNA1 and siRNA2) were used for each metastasis suppressor. Two time points (48hr and 96hr) were considered as end of transfection in order to measure early and late effects of the metastasis suppressors downregulation.

2013-12-27 | E-GEOD-53668 | biostudies-arrayexpress

Adipose MSC suppress breast cancer progression, metastasis and inhibit EMT pathways via exosomal-miRNAs following co-culture interaction

Project description:Introduction: Mesenchymal stem cells (MSCs) are commonly known to influence the progression of cancer due to their ability to migrate to the tumor microenvironment and interact with cancer cells. Exosomes have been found secreted by most cell types and have been shown to act as cargo carrying biomolecules including microRNA (miRNAs). Thus, understanding interaction between MSCs and cancer cells via exosomal miRNAs is crucial in determining the therapeutic role of MSC in treating breast cancer cells and relapse. Methods: Exosomes were harvested from the medium of indirect co-culture of MCF7-luminal and MDA-MB-231-basal breast cancer cells (BCCs) subtypes with adipose MSCs and profiled for miRNAs using next-generation sequencing. Results: The interaction resulted in the changes of exosomal miRNAs profiles that modulate essential signalling pathways and cell cycle arrest into dormancy via inhibition of epithelial-to-mesenchymal transition (EMT). The maintenance and induction of epithelial features in MCF7 and MDA cells have led to a positive correlation with the reduction of proliferation and metastasis as well as increased drug resistance. Overall, adipose MSCs mediated delivery of consensus miRNAs particularly miR-200 family in MCF7, miR-146a in MDA and miR-941 in both BCCs subtypes via exosomes.

2020-08-18 | GSE156380 | GEO

miR-100 maintains phenotype of tumor associated macrophages by targeting mTOR to promote tumor metastasis via Stat5a/IL-1ra pathway in mouse breast cancer

Project description:Tumor-associated macrophages (TAMs)，the main part of immune cells in tumor microenvironment (TME)，play a potent role in promoting tumorigenesis through mechanisms such as stimulating angiogenesis, enhancing tumor migration and suppressing antitumor immunity. MicroRNAs (miRNAs) are considered as crucial regulators in multiple biological processes. The relationship between miRNAs and macrophages function has been extensively reported, but the roles that miRNAs play in regulating TAMs phenotype remains unclear. In this study, we screened highly-expressed microRNAs in TAMs, and first identified that miR-100 represented a TAMs-high expression pattern and maintained TAMs phenotype by targeting mTOR signaling pathway. Moreover, miR-100 expression level in TAMs was positively related to IL-1ra secretion, a traditional immune-suppressive cytokine, which was determined to promote tumor cells stemness via stimulating Hedgehog pathway. Mechanism study suggested that mTOR/Stat5a pathway was involved in IL-1ra transcriptional regulation process mediated by miR-100. More importantly, tumor metastasis and invasion capacity were significantly decreased in a 4T1 mouse breast cancer model injected intratumorally with miR-100 antagomir, and combination therapy with cisplatin showed much better benefit. In this study, we confirmed that highly expressed miR-100 maintains the phenotype of TAMs and promotes tumor metastasis via enhancing IL-1ra secretion. Interfering miR-100 expression of TAMs in mouse breast cancer model could inhibit TAMs pro-tumor function and reduce tumor metastasis, which suggested that miR-100 could serve as a potential therapy target to remodel tumor microenvironment in breast cancer.

2019-06-03 | GSE115295 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

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