MiR-210 is induced by Oct-2, regulates B-cells and inhibits autoantibody production
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE48186 | GEO | 2013/06/21
SECONDARY ACCESSION(S): PRJNA209126
REPOSITORIES: GEO
Similar Datasets
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: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: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: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. KYSE-170 cells were transfected with oligoribonucleotides for miR-210 or ncRNA (Ambion, Austin, TX) using Hiperfect (Qiagen, Valencia, CA) according to the provider’s protocol for overexpression. Total RNA was extracted by the acid guanidinium thiocyanate-phenol-chloroform method and was labeled and prepared for hybridization to human Oligo chip 25k (Toray, Kamakura, Japan) using standard methods.
2011-01-05 | E-GEOD-20637 | 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. Previously, we demonstrated that miR-210 is a key player of endothelial cell (EC) response to hypoxia, modulating EC survival, migration and ability to form capillary like-structures. Moreover, the receptor tyrosine kinase ligand Ephrin-A3 was identified as one functionally relevant target. Since each miRNA regulates hundreds of mRNAs, different approaches were combined to identify new miR-210 targets: a Using target prediction software, 32 new miR-210 potential targets were identified. b The proteomic profiling of miR-210 over-expressing ECs identified 11 proteins that were specifically inhibited by miR-210, either directly or indirectly. c Affymetrix based gene expression profiles identified 51 genes that were both down-modulated by miR-210 over-expression and de-repressed when miR-210 was blocked. Surprisingly, only few genes identified either by proteomics or transcriptomics were recognized as miR-210 targets by target prediction algorithms. However, a low-stringency pairing research revealed enrichment for miR-210 putative binding sites, raising the possibility that these genes were targeted via non-canonical recognition sequences. To clarify this issue, miR-210-loaded RISC was purified by immuno-precipitation along with its mRNA targets. The presence of Ephrin-A3 mRNA in the complex validated this approach. We found that 32 potential targets were indeed enriched in miR-210-loaded RISC, and thus can be considered as genuine miR-210 targets. In keeping with this conclusion, we were able to further validate a sub-set of them by 3’UTR-reporter assays. Gene ontology analysis of the targets confirmed the known miR-210 activity in differentiation and cell cycle regulation, highlighting new functions such as involvement in RNA processing, DNA binding, development, membrane trafficking and amino acid catabolism. In conclusion, we validated a multidisciplinary approach for miRNAs target identification and indicated novel molecular mechanisms underpinning miR-210 role in EC response to hypoxia.
2009-10-27 | GSE16962 | 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. Previously, we demonstrated that miR-210 is a key player of endothelial cell (EC) response to hypoxia, modulating EC survival, migration and ability to form capillary like-structures. Moreover, the receptor tyrosine kinase ligand Ephrin-A3 was identified as one functionally relevant target. Since each miRNA regulates hundreds of mRNAs, different approaches were combined to identify new miR-210 targets: a Using target prediction software, 32 new miR-210 potential targets were identified. b The proteomic profiling of miR-210 over-expressing ECs identified 11 proteins that were specifically inhibited by miR-210, either directly or indirectly. c Affymetrix based gene expression profiles identified 51 genes that were both down-modulated by miR-210 over-expression and de-repressed when miR-210 was blocked. Surprisingly, only few genes identified either by proteomics or transcriptomics were recognized as miR-210 targets by target prediction algorithms. However, a low-stringency pairing research revealed enrichment for miR-210 putative binding sites, raising the possibility that these genes were targeted via non-canonical recognition sequences. To clarify this issue, miR-210-loaded RISC was purified by immuno-precipitation along with its mRNA targets. The presence of Ephrin-A3 mRNA in the complex validated this approach. We found that 32 potential targets were indeed enriched in miR-210-loaded RISC, and thus can be considered as genuine miR-210 targets. In keeping with this conclusion, we were able to further validate a sub-set of them by 3âUTR-reporter assays. Gene ontology analysis of the targets confirmed the known miR-210 activity in differentiation and cell cycle regulation, highlighting new functions such as involvement in RNA processing, DNA binding, development, membrane trafficking and amino acid catabolism. In conclusion, we validated a multidisciplinary approach for miRNAs target identification and indicated novel molecular mechanisms underpinning miR-210 role in EC response to hypoxia. Experiment Overall Design: Gene expression modifications induced by both miR-210 over-expression and blockade were evaluated. In order to identify new direct and indirect miR-210 targets, transcripts repressed by miR-210 over-expression and up-regulated by miR-210 inhibition (and vice versa) were selected.
2009-11-07 | E-GEOD-16962 | biostudies-arrayexpress
Project description:Cl-amidine treatment reduces autoantibody responses in CIA. Sera were collected from Cl-amidine and control treated mice, and autoantibodies in these samples were profiled using Synovial Antigen Arrays. Significance Analysis of Microarrays (SAM) was used to analyze the antigen array datasets, and identified 8 antigens with a significant difference in autoantibody reactivity (false discovery rate (q) < 5%). Hierarchical clustering was then performed to elucidate the relationships between the autoantibody profiles. The Cl-amidine treated mice clustered together and exhibited lower autoantibody titers against all of the 8 antigens identified by SAM, including autoantibody reactivity to native epitopes derived from cartilage as well as citrulline-modified filaggrin peptides.
2010-08-21 | GSE23731 | GEO
Project description:Compulsory expression of miR-210 in normal endometrial stromal cells directed the induction of cell proliferation and vascular endothelial growth factor production, and the inhibition of apoptosis in through signal transducer and activator of transcription 3 (STAT3) activation. Accumulating evidence suggests that microRNAs play definite roles in the pathogenesis of endometriosis. The objective of the study was to determine the role of miR-210, one of the upregulated microRNA in endometriotic cyst stromal cells, in the pathogenesis of endometriosis. Downstream targets of miR-210 were identified by Compulsory expression of miR-210 in normal eutopic endometrial stromal cells, a global mRNA microarray technique, and Ingenuity pathways analysis.
2015-04-06 | GSE56854 | GEO
Project description:Glaucoma is the leading cause of irreversible blindness worldwide. An early diagnosis of the disease is crucial for treatment success. Mechanisms behind glaucoma pathogenesis are not completely understood, but disease related alterations in the serological autoantibody profile indicate an immunologic component. These changes in immunoreactivity may serve as potential biomarkers. Therefore, a serological proteome analysis (SERPA) approach was used to identify novel autoantibody biomarker candidates in primary open angle glaucoma. Autoantibodies in individual sera samples of glaucoma patients and control were analysed by serological proteome analysis (SERPA) using porcine trabecular meshwork (TM) tissue lysates as antigen source. Immunoblot spot intensities were computed by “Delta2D” (Decodon) and spots of interest were matched with preparative 2DE gels and identified by mass spectrometry to identify the potential autoantigens.
2019-02-21 | PXD011752 | Pride
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