Global MicroRNA Expression Profiling Identifies MiR-210 Associated with Tumor Proliferation, Invasion and Poor Clinical Outcome in Breast Cancer
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ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Françoise Rothé
PROVIDER: E-GEOD-28321 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:In order to improve our understanding of breast cancer (BC) biology and its prognostication, global miRNA expression profiling was performed using microarray technology on systemically untreated BC patients with long-term follow up.
2011-07-01 | GSE28321 | GEO
Project description:Our recent study of gene expression in mice treated with LPS systemically identified the E2F1 transcription factor as a novel regulator of innate immune response in lung, liver, and spleen tissue. Our follow up studies showed that RNAi-mediated inhibition or E2F1 gene deficiency lead to reduced inflammatory response to LPS in vitro and in vivo. Furthermore, a clear role for the role of miRNAs in the regulation of innate immune response to LPS has emerged. In the current study, we further examined B6;129E2F1-/- and B6x126 F2 mice in the systemic LPS model and used gene expression profiling to identify a defect in the coagulation cascade that contributes to increased morbidity of B6;129E2F1-/- mice despite their reduced systemic inflammatory response. We also studied miRNA expression profiles identified miRNAs that are differentially expressed in B6;129E2F1-/- but not B6x129 F2 mice. 32 mice (4-6) per group, E2F+/+ or E2F-/- genotype, treated with saline or LPS, 6 or 20 hrs
2012-06-30 | E-GEOD-33900 | biostudies-arrayexpress
Project description:Our recent study of gene expression in mice treated with LPS systemically identified the E2F1 transcription factor as a novel regulator of innate immune response in lung, liver, and spleen tissue. Our follow up studies showed that RNAi-mediated inhibition or E2F1 gene deficiency lead to reduced inflammatory response to LPS in vitro and in vivo. Furthermore, a clear role for the role of miRNAs in the regulation of innate immune response to LPS has emerged. In the current study, we further examined B6;129E2F1-/- and B6x126 F2 mice in the systemic LPS model and used gene expression profiling to identify a defect in the coagulation cascade that contributes to increased morbidity of B6;129E2F1-/- mice despite their reduced systemic inflammatory response. We also studied miRNA expression profiles identified miRNAs that are differentially expressed in B6;129E2F1-/- but not B6x129 F2 mice. 32 mice (4-6) per group, E2F+/+ or E2F-/- genotype, treated with saline or LPS, 6 or 20 hrs
2012-06-30 | E-GEOD-33901 | biostudies-arrayexpress
Project description:Brain metastasis (BM) can affect up to 25% of non-small cell lung cancer (NSCLC) patients during their lifetime. Efforts to characterize patients that will develop BM have been fairly disappointing. Small non-coding microRNAs (miRNAs) regulate the expression of target mRNAs by repressing their translation or regulating their sequence-specific degradation. miRNAs play a role in regulating a variety of targets and, consequently, multiple pathways, which makes them a powerful tool to be exploited for early detection of disease, risk assessment, and prognosis. In this study, we investigated miRNAs that may serve as biomarkers to differentiate between NSCLC patients with and without BM. miRNA microarray profiling was performed on samples from clinically matched NSCLC from patients with BM (BM+) and without BM (BM-). miR-328 and miR-330-3p were able to correctly classify BM+ vs. BM- patients. Gene expression analysis comparing NSCLC parental and stably transfected miR-328 cells identified several significantly differentially-expressed genes, whose expression may be directly or indirectly regulated by miR-328. NSCLC Cell Line A549 analysis: Two-condition experiment, A549 GFP Control vs. A549 miR-328 cells. Biological replicates: 2 control replicates, 2 miR-328 replicates. miRNA microarray analysis was performed on RNA extracted from formalin-fixed paraffin-embedded (FFPE) NSCLC tumor specimens from 7 BM+ patients and 5 BM- patients.
2011-02-16 | E-GEOD-23019 | biostudies-arrayexpress
Project description:As miR-210 expression is correlated to poor prognosis both in estrogen-positive and in estrogen-negative breast cancer (BC) patients, we aimed to investigate the biological processes regulated by miR-210 and which may elucidate its function in the aggressive phenotype of high grade breast cancer. We performed in silico functional analyses of the genes deregulated upon miR-210 overexpression in MCF7 BC cell line and upon miR-210 repression in MDA-MB-231 BC cell line using lentiviral transduction. Gene expression profiling analysis of these cells revealed the deregulation of genes involved in several biological pathways including cell adhesion, extracellular structure organization, epithelial cell proliferation, cell division, cell cycle and immune response.
2011-07-01 | GSE25162 | GEO
Project description:As miR-210 expression is correlated to poor prognosis both in estrogen-positive and in estrogen-negative breast cancer (BC) patients, we aimed to investigate the biological processes regulated by miR-210 and which may elucidate its function in the aggressive phenotype of high grade breast cancer. We performed in silico functional analyses of the genes deregulated upon miR-210 overexpression in MCF7 BC cell line and upon miR-210 repression in MDA-MB-231 BC cell line using lentiviral transduction. Gene expression profiling analysis of these cells revealed the deregulation of genes involved in several biological pathways including cell adhesion, extracellular structure organization, epithelial cell proliferation, cell division, cell cycle and immune response. MCF-7 cells overexpressing miR-210 (or control) and MDA-MB-231 cells in which miR-210 (or control) is repressed were used for RNA extraction and hybridization on Affymetrix microarrays.
2011-07-01 | E-GEOD-25162 | biostudies-arrayexpress
Project description:Epidemiological evidence has identified an association between breast cancer (BC) and systemic dysregulation of glucose metabolism. However, how BC influences glucose homeostasis remains unknown. Here we show that BC-derived extracellular vesicles (EVs) suppress pancreatic endocrine secretion to systemically reset glucose homeostasis. In pancreatic β-cells, miR-122 delivered in BC-derived EVs targets PKM to suppress glycolysis and ATP-dependent insulin exocytosis. Mice receiving high-miR-122 EVs or bearing BC xenograft tumors, but not those with tumors deficient in EV secretion or miR-122, exhibit suppressed insulin secretion, enhanced endogenous glucose production, impaired glucose tolerance, and hyperglycemia. Compared to non-cancer controls, BC patients have higher levels of EV-encapsulated miR-122 and fasting glucose but lower insulin levels in blood; the miR-122 levels are positively associated with glucose and negatively associated with insulin. This EV-mediated glucose reallocation at the whole-body level may contribute to tumor growth and progression, as well as higher incidence of diabetes in BC patients.
2021-08-01 | GSE173276 | GEO
Project description:Estrogen Receptor B (ERB) is a member of the nuclear receptor family of homeostatic regulators that is frequently lost in breast cancer (BC), where its presence correlates with a better prognosis and a less aggressive clinical outcome of the disease. Contrary to ERα, its closest homolog, ERB shows also significant estrogen-independent activities, including the ability to inhibit cell cycle progression and to regulate gene transcription in the absence of the ligand. Investigating the nature and extent of this constitutive activity of ERB in BC MCF-7 cells by miRNA-Seq, we identified 127 miRNAs differentially expressed in ERB+ vs ERB- cells in the absence of ligand, including upregulated oncosuppressor miRs, such miR-30a, and downregulated onco-miRs, like miR-21. In addition, a significant fraction of >1,600 unique proteins identified in these cells by iTRAQ (isobaric Tag for Relative and Absolute Quantitation) quantitative proteomics was either increased or decreased by ERB, revealing regulation of multiple cell pathways by ligand-free receptor. Transcriptome analysis indicates that for a large number of proteins regulated by ERB the corresponding mRNAs are unaffected, including a large number of putative targets of ERB-regulated miRNAs, indicating a central role of miRNAs in mediating BC cell proteome regulation by ERB. Expression of a mimic of miR-30a-5p, a direct target and downstream effector of ERB in BC, led to the identification of several target transcripts of this miRNA, including 11 encoding proteins whose intracellular concentration is significantly affected by unliganded receptor. These results demonstrate a significant effect of ligand-free ERB on BC cell functions via modulation of the cell proteome and suggest that miRNA regulation may represent a key event in the control of the biological and clinical phenotype of hormone-responsive BC by this nuclear receptor.
2014-10-23 | PXD000499 | Pride
Project description:Brain metastasis (BM) can affect up to 25% of non-small cell lung cancer (NSCLC) patients during their lifetime. Efforts to characterize patients that will develop BM have been fairly disappointing. Small non-coding microRNAs (miRNAs) regulate the expression of target mRNAs by repressing their translation or regulating their sequence-specific degradation. miRNAs play a role in regulating a variety of targets and, consequently, multiple pathways, which makes them a powerful tool to be exploited for early detection of disease, risk assessment, and prognosis. In this study, we investigated miRNAs that may serve as biomarkers to differentiate between NSCLC patients with and without BM. miRNA microarray profiling was performed on samples from clinically matched NSCLC from patients with BM (BM+) and without BM (BM-). miR-328 and miR-330-3p were able to correctly classify BM+ vs. BM- patients. Gene expression analysis comparing NSCLC parental and stably transfected miR-328 cells identified several significantly differentially-expressed genes, whose expression may be directly or indirectly regulated by miR-328.
2011-02-16 | GSE23019 | GEO
Project description:Recent studies have identified miR-210 among a set of hypoxia-regulated miRNAs, and shown the central regulatory role played by HIF to control transcription of this miRNA. Contradictory data exist concerning the regulation and roles of miR-210 during cancer progression. miR-210 appears at the same time over-expressed in some solid tumors (breast, pancreas, head and neck carcinomas, gliomas) while often deleted in ovarian carcinoma. It has been shown that depending on the tissue type or cellular model, miR-210 was indeed able to either promote entry into the cell cycle and to inhibit apoptosis or rather repress tumor initiation. We show here deregulation of several miRNAs in human lung cancer biopsies, including an over-expression of miR-210 which appears specific of late-stages of the tumor (>stage 2). MiR-210 function was then analyzed in the lung adenocarcinoma cell line A549. We found that miR-210 induced a delayed inhibition of proliferation associated with an induction of cell death. We also observed that mir-210 induces a loss of mitochondrial membrane potential and the apparition of an aberrant mitochondrial phenotype. mRNA expression profiling of cells overexpressing mir-210 revealed a specific signature characterized by an enrichment in mir-210 predicted targets among the downregulated transcripts (57 out of 243, p<10-12). Functional annotation of this set of mir-210-regulated transcripts, which includes several subunits of Electron Transport Chain (ETC) complex I and complex II revealed enrichment for terms such as 'cell death' and 'mitochondrial dysfunction'. Two of these ETC subunits, predicted to be targets of mir-210 by several bioinformatics prediction tools, were experimentally confirmed after cloning of their respective 3'UTR in a luciferase reporter vector. Finally, we provide experimental evidence indicating that these mitochondrial alterations could modulate HIF via a positive regulatory loop. Overall, our data strongly suggest that mir-210 could mediate two apparently opposite functions: i) apoptosis through targeting of specific mitochondrial components ii) a modulation of HIF through a positive regulatory loop. We propose that this dual behavior can explain the contradictory data regarding the impact of miR-210 during cancer progression. Refer to individual Series. This SuperSeries is composed of the following subset Series: GSE18692: MiRNA and lung cancer (INCA project) - 40 miRNAs microarrays GSE18694: MiRNA and lung cancer (INCA project) - 26 RNG25k microarrays GSE18695: MiRNA and lung cancer (INCA Project) - 66 RNG25k microarrays
2010-09-30 | E-GEOD-18805 | biostudies-arrayexpress