Functional analyses of miR-210 involvement in the aggressive phenotype of high grade breast tumors
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE25162 | GEO | 2011/07/01
SECONDARY ACCESSION(S): PRJNA134355
REPOSITORIES: GEO
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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:MicroRNAs (miRNAs) are small non-protein-coding RNAs that are incorporated into the RNA-induced silencing complex (RISC) and inhibit gene expression by regulating the stability and/or the translational efficiency of target mRNAs. miR-210 can be considered a master miRNA of hypoxic response and is currently regarded as a promising novel non-invasive tumor hypoxia marker. The targets identified to date indicate that miR-210 plays a role in cell cycle regulation, differentiation, mitochondrial metabolism repression, DNA repair and apoptosis. In order to identify miRNAs sub-sequentely modulated by miR-210, miRNA expression profiles of human umbilical vein endothelial cells (HUVEC) over-expressing miR-210 were generated, allowing the identification of miRNAs modulated upon miR-210 up-regulation. HUVEC over-expressing pre-miR-210 or a scramble sequence were generated by retroviral infection, yielding a selected population that expressed mature miR-210 levels comparable with those observed in hypoxic cells. miRNA expression profiles were then measured and miRNAs modulated upon miR-210 up-regulation were identified. This Sample represents four hybridizations - one of which was a dye-swap.
2015-01-01 | E-GEOD-35365 | biostudies-arrayexpress
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. This SuperSeries is composed of the SubSeries listed below.
2010-10-01 | GSE18805 | GEO
Project description:MicroRNAs (miRNAs) are small non-protein-coding RNAs that are incorporated into the RNA-induced silencing complex (RISC) and inhibit gene expression by regulating the stability and/or the translational efficiency of target mRNAs. miR-210 can be considered a master miRNA of hypoxic response and is currently regarded as a promising novel non-invasive tumor hypoxia marker. The targets identified to date indicate that miR-210 plays a role in cell cycle regulation, differentiation, mitochondrial metabolism repression, DNA repair and apoptosis. In order to identify miRNAs sub-sequentely modulated by miR-210, miRNA expression profiles of human umbilical vein endothelial cells (HUVEC) over-expressing miR-210 were generated, allowing the identification of miRNAs modulated upon miR-210 up-regulation.
2015-01-01 | GSE35365 | GEO
Project description:mRNA profiling of miR-210 transgenic (in vivo), mimic-transfected (in vitro) and miR-210 knockout activated mouse B-cells was performed to assess the effect of miR-210 overexpression on the B-cell transcriptome.
2013-08-23 | E-MTAB-1758 | biostudies-arrayexpress
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
Project description:The resistance of hypoxic cells to radiotherapy and chemotherapy is a major problem in the treatment of cancer. Recently, an additional level of Hypoxia Inducible Factor (HIF) dependent transcriptional regulation has emerged involving modulation of a specific set of miRNAs including miR-210. We have recently shown that HIF-1 induction of miR-210 also stabilizes HIF-1 through a positive regulatory loop. We therefore hypothesized that by stabilizing HIF-1 in normoxia, miR-210 may protect cancer cells from radiation. We developed Non-Small Cell Lung Cancer (NSCLC)-derived cell lines (A549 and H1975) stably expressing miR-210 (pmiR-210) or a control miRNA (pmiR-Ctl). MiR-210 expressing cells showed a significant stabilization of HIF-1 associated with mitochondrial defects and a glycolytic phenotype. The cells were subjected to radiation levels ranging from 0 to 10Gy in normoxia and hypoxia. Cells expressing miR-210 in normoxia had the same level of resistance than control cells in hypoxia. pmiR-210 cells under hypoxia showed a low mortality rate due to a decrease in apoptosis and an ability to grow even at 10Gy. We have established that radioresistance was independent of p53 and cell cycle status. In addition, we show here that genomic double strand breaks (DSB) foci disappeared faster in pmiR-210 than in pmiR-Ctl cells, suggesting that miR-210 expression promotes a more efficient DSB repair. Finally, HIF-1 invalidation in pmiR-210 cells (pmiR-210/HIF-1-) abolished radioresistance of cells showing that this mechanism was dependent upon HIF-1. In conclusion, miR-210 appears to be a major component in the radioresistance of hypoxic cancer cells. Given the high stability of most miRNAs, this advantage could even be used by tumor cells in conditions where hypoxia may not be present anymore and strongly suggests that strategies targeting miR-210 would enhance tumor radiosensitization.
2013-04-01 | GSE43622 | GEO
Project description:MicroRNAs are small, non-coding RNAs that regulate gene expression post-transcriptionally. Here, we show that miR-210 is induced by Oct-2, a key transcriptional mediator of B-cell activation. Germline deletion of miR-210 results in the development of autoantibodies from 5 months of age. Overexpression of miR-210 in vivo resulted in cell autonomous expansion of the B1 lineage and impaired fitness of B2 cells. Mice over-expressing miR-210 exhibited impaired class-switched antibody responses, a finding confirmed in wild-type B-cells transfected with a miR-210 mimic. In vitro studies demonstrated a defect in cellular proliferation and cell-cycle entry, which was consistent with the transcriptomic analysis demonstrating down-regulation of genes involved in cellular proliferation and B cell activation. These findings indicate that Oct-2 induction of miR-210 provides a novel inhibitory mechanism for the control of B cells and autoantibody production. Splenic B-cells from different mouse strains were stimulated with either anti-IgM, CD40L and IL-4 or LPS for 48 hours Treatments: rest (unstimulated), Fab/Fab2 (=anti-IgM + CD40L + IL-4), LPS. There is no difference between Fab and Fab2 stimulation conditions. The goal of this study was to look for activation-induced microRNA changes upon B-cell activation, of which miR-210 was one of them.
2013-06-21 | E-GEOD-48186 | biostudies-arrayexpress
Project description:MicroRNAs are small non-coding RNA species, some of which are playing important roles in malignancies. However, roles of miR-210 in cancer have yet to be unknown and controversial. Here, we found the expression level of miR-210 is downregulated in human esophageal squamous cell carcinoma and its cell lines. Additionally, we demonstrate that miR-210 inhibits cancer cell survival and proliferation through upregulation of cell death and induction of cell cycle arrest at G1/G0 and G2/M phases. However, candidate target mRNAs of miR-210 and the mechanism behind observed phenomena is uncertain. Then, we performed comprehensive gene expression analysis to identify candidate target mRNAs and understand their mechanisms.
2011-01-05 | GSE20637 | GEO
Project description:Single microRNAs are usually associated with hundreds of putative target genes that can influence multiple phenotypic traits in Drosophila, ranging from development to behaviour. We investigated the function of Drosophila miR-210 in circadian behaviour by misexpressing it within circadian clock cells. Manipulation of miR-210 expression levels in the PDF (pigment dispersing factor) positive neurons affected the phase of locomotor activity, under both light-dark conditions and constant darkness. PER cyclical expression was not affected in clock neurons, however, when miR-210 was up-regulated, a dramatic alteration in the morphology of PDF ventral lateral neuron (LNv) arborisations was observed. The effect of miR-210 in shaping neuronal projections was confirmed in vitro, using a Drosophila neuronal cell line. A transcriptomic analysis revealed that miR-210 overexpression affects the expression of several genes belonging to pathways related to circadian processes, neuronal development, GTPases signal transduction and photoreception. Collectively, these data reveal the role of miR-210 in modulating circadian outputs in flies and guiding/remodelling PDF positive LNv arborisations and indicate that miR-210 may have pleiotropic effects on the clock, light perception and neuronal development.
2018-11-13 | GSE77245 | GEO