Identification of dynamically regulated microRNA and mRNA networks in developing oligodendrocytes.
Ontology highlight
ABSTRACT:
SUBMITTER: Lau P
PROVIDER: S-EPMC2646797 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:MicroRNAs (miRNAs) play important roles in modulating gene expression at the post-transcriptional level. In postnatal oligodendrocytes, the miRNA expression profile -“microRNAome” - consists of 98 miRNAs whose expression dynamically changes during the transition from A2B5+ oligodendrocyte progenitor cells to premyelinating GalC+ cells. The combination of microRNAome profiling with analyses of the oligodendrocyte transcriptome reveals a target bias for a class of miRNAs which includes miR-9. We show that miR-9 is down-regulated during oligodendrocyte differentiation. In addition, miR-9 expression levels inversely correlate with the expression of its predicted targets, among which is the peripheral myelin protein, PMP22. PMP22 mRNA but not protein is detectable in oligodendrocytes, while Schwann cells producing PMP22 protein lack miR-9. We demonstrate that miR-9 interacts with the 3’ untranslated region of PMP22 and down-regulates its expression. Our results support models in which miRNAs can act as guardians of the transcriptome. Keywords: developmental stage
2008-06-01 | GSE11218 | GEO
Project description:BackgroundMiRNAs are essential mediators of many biological processes. The aim of this study was to investigate the dynamics of miRNA-mRNA regulatory networks during exercise and the subsequent recovery period.ResultsHere we monitored the transcriptome changes using microarray analysis of the whole blood of eight highly trained athletes before and after 30 min of moderate exercise followed by 30 min and 60 min of recovery period. We combined expression profiling and bioinformatics and analysed metabolic pathways enriched with differentially expressed mRNAs and mRNAs which are known to be validated targets of differentially expressed miRNAs. Finally we revealed four dynamically regulated networks comprising differentially expressed miRNAs and their known target mRNAs with anti-correlated expression profiles over time. The data suggest that hsa-miR-21-5p regulated TGFBR3, PDGFD and PPM1L mRNAs. Hsa-miR-24-2-5p was likely to be responsible for MYC and KCNJ2 genes and hsa-miR-27a-5p for ST3GAL6. The targets of hsa-miR-181a-5p included ROPN1L and SLC37A3. All these mRNAs are involved in processes highly relevant to exercise response, including immune function, apoptosis, membrane traffic of proteins and transcription regulation.ConclusionsWe have identified metabolic pathways involved in response to exercise and revealed four miRNA-mRNA networks dynamically regulated following exercise. This work is the first study to monitor miRNAs and mRNAs in parallel into the recovery period. The results provide a novel insight into the regulatory role of miRNAs in stress adaptation.
| S-EPMC3681679 | biostudies-literature
Project description:MiRNAs are essential mediators of many biological processes. The aim of this study was to investigate the dynamics of miRNA-mRNA regulatory networks during exercise and subsequent recovery period. Here we monitored the transcriptome changes by microarray analysis of the whole blood of eight highly trained athletes after 30 min of moderate exercise followed by 30 min and 60 min of recovery period. We combined expression profiling and bioinformatics and analysed metabolic pathways enriched with differentially expressed mRNAs and then mRNAs which are known to be validated targets of differentially expressed miRNAs. Finally we revealed four dynamically regulated networks comprising differentially expressed miRNAs and their known target mRNAs with anti-correlated expression profiles over time. The data suggest that hsa-miR-21-5p regulated TGFBR3, PDGFD and PPM1L mRNAs. Hsa-miR-24-2-5p was likely to be responsible for MYC and KCNJ2 genes and hsa-miR-27a-5p for ST3GAL6. The targets of hsa-miR-181a-5p included ROPN1L and SLC37A3. All these mRNAs are involved in processes highly relevant to exercise response, including immune function, apoptosis, membrane traffic of proteins and transcription regulation. We have identified four miRNA-mRNA networks dynamically regulated following exercise. This work is the first study to monitor miRNAs and mRNAs in parallel into recovery period. The results provide a novel insight into the regulatory role of miRNAs in stress adaptation. Each subject performed a treadmill test with an incremental step protocol until exhaustion. Blood samples were taken from the antecubital vein using indwelling catheter before (T1), immediately after ramp test to exaustion (T2) and after 30 min of recovery (T3). Two weeks later, athletes participated in the main exercise, consisting of running at 80% VO2 peak for 30 min on a treadmill. Blood samples were taken from the antecubital vein using indwelling catheter before (T4), immediately after running at 80% VO2 peak for 30 min on a treadmill (T5), after 30 min (T6) and 60 min (T7) of recovery.
2013-04-30 | E-GEOD-46075 | biostudies-arrayexpress
Project description:MicroRNAs (miRNAs) play important roles in modulating gene expression at the post-transcriptional level. In postnatal oligodendrocytes, the miRNA expression profile -â??microRNAomeâ?? - consists of 98 miRNAs whose expression dynamically changes during the transition from A2B5+ oligodendrocyte progenitor cells to premyelinating GalC+ cells. The combination of microRNAome profiling with analyses of the oligodendrocyte transcriptome reveals a target bias for a class of miRNAs which includes miR-9. We show that miR-9 is down-regulated during oligodendrocyte differentiation. In addition, miR-9 expression levels inversely correlate with the expression of its predicted targets, among which is the peripheral myelin protein, PMP22. PMP22 mRNA but not protein is detectable in oligodendrocytes, while Schwann cells producing PMP22 protein lack miR-9. We demonstrate that miR-9 interacts with the 3â?? untranslated region of PMP22 and down-regulates its expression. Our results support models in which miRNAs can act as guardians of the transcriptome. Experiment Overall Design: Flow cytometry was used to isolate single A2B5+ and single GalC+ oligodedrocytes from postnatal day 7 rat whole brain. 4 biological replicates were obtained for each group using a pooled litter of 10 pups per biological replicate
2008-06-18 | E-GEOD-11218 | biostudies-arrayexpress
Project description:MiRNAs are essential mediators of many biological processes. The aim of this study was to investigate the dynamics of miRNA-mRNA regulatory networks during exercise and subsequent recovery period. Here we monitored the transcriptome changes by microarray analysis of the whole blood of eight highly trained athletes after 30 min of moderate exercise followed by 30 min and 60 min of recovery period. We combined expression profiling and bioinformatics and analysed metabolic pathways enriched with differentially expressed mRNAs and then mRNAs which are known to be validated targets of differentially expressed miRNAs. Finally we revealed four dynamically regulated networks comprising differentially expressed miRNAs and their known target mRNAs with anti-correlated expression profiles over time. The data suggest that hsa-miR-21-5p regulated TGFBR3, PDGFD and PPM1L mRNAs. Hsa-miR-24-2-5p was likely to be responsible for MYC and KCNJ2 genes and hsa-miR-27a-5p for ST3GAL6. The targets of hsa-miR-181a-5p included ROPN1L and SLC37A3. All these mRNAs are involved in processes highly relevant to exercise response, including immune function, apoptosis, membrane traffic of proteins and transcription regulation. We have identified four miRNA-mRNA networks dynamically regulated following exercise. This work is the first study to monitor miRNAs and mRNAs in parallel into recovery period. The results provide a novel insight into the regulatory role of miRNAs in stress adaptation.
2013-04-30 | GSE46075 | GEO
Project description:The assembly of a mature vascular network involves coordinated endothelial cell (EC) shape changes, including the process of EC elongation. How EC elongation is dynamically regulated in vivo is not fully understood. Here, we have generated a zebrafish mutant that is deficient for the integrin adaptor protein Talin 1 (Tln1). Using a new focal adhesion (FA) marker line expressing endothelial Vinculinb-eGFP, we demonstrate that EC FAs function dynamically and are lost in our tln1 mutants, allowing us to uncouple the primary roles of FAs in EC morphogenesis from the secondary effects that occur due to systemic vessel failure or loss of blood flow. Tln1 loss led to compromised F-actin rearrangements, perturbed EC elongation and disrupted cell-cell junction linearisation in vessel remodelling. Finally, chemical induction of actin polymerisation restored actin dynamics and EC elongation during vascular morphogenesis. Together, we identify that FAs are essential for EC elongation and junction linearisation in flow-pressured vessels and that they influence actin polymerisation in cellular morphogenesis. These observations can explain the severely compromised vessel beds and vascular leakage observed in mutant models that lack integrin signalling. This article has an associated 'The people behind the papers' interview.
| S-EPMC10214536 | biostudies-literature
Project description:MicroRNAs (miRNAs) and transcription factors control eukaryotic cell proliferation, differentiation, and metabolism through their specific gene regulatory networks. However, differently from transcription factors, our understanding of the processes regulated by miRNAs is currently limited. Here, we introduce gene network analysis as a new means for gaining insight into miRNA biology. A systematic analysis of all human miRNAs based on Co-expression Meta-analysis of miRNA Targets (CoMeTa) assigns high-resolution biological functions to miRNAs and provides a comprehensive, genome-scale analysis of human miRNA regulatory networks. Moreover, gene cotargeting analyses show that miRNAs synergistically regulate cohorts of genes that participate in similar processes. We experimentally validate the CoMeTa procedure through focusing on three poorly characterized miRNAs, miR-519d/190/340, which CoMeTa predicts to be associated with the TGF? pathway. Using lung adenocarcinoma A549 cells as a model system, we show that miR-519d and miR-190 inhibit, while miR-340 enhances TGF? signaling and its effects on cell proliferation, morphology, and scattering. Based on these findings, we formalize and propose co-expression analysis as a general paradigm for second-generation procedures to recognize bona fide targets and infer biological roles and network communities of miRNAs.
| S-EPMC3371699 | biostudies-literature
Project description:BackgroundPeriodontitis is a complex infectious disease with various causes and contributing factors. The aim of this study was to identify key genes, microRNAs (miRNAs) and transcription factors (TFs) and construct a miRNA-mRNA-TF regulatory networks to investigate the underlying molecular mechanism in periodontitis.MethodsThe GSE54710 miRNA microarray dataset and the gene expression microarray dataset GSE16134 were downloaded from the Gene Expression Omnibus database. The differentially expressed miRNAs (DEMis) and mRNAs (DEMs) were screened using the "limma" package in R. The intersection of the target genes of candidate DEMis and DEMs were considered significant DEMs in the regulatory network. Next, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted. Subsequently, DEMs were uploaded to the STRING database, a protein-protein interaction (PPI) network was established, and the cytoHubba and MCODE plugins were used to screen out key hub mRNAs and significant modules. Ultimately, to investigate the regulatory network underlying periodontitis, a global triple network including miRNAs, mRNAs, and TFs was constructed using Cytoscape software.Results8 DEMis and 121 DEMs were found between the periodontal and control groups. GO analysis showed that mRNAs were most significantly enriched in positive regulation of the cell cycle, and KEGG pathway analysis showed that mRNAs in the regulatory network were mainly involved in the IL-17 signalling pathway. A PPI network was constructed including 81 nodes and 414 edges. Furthermore, 12 hub genes ranked by the top 10% genes with high degree connectivity and five TFs, including SRF, CNOT4, SIX6, SRRM3, NELFA, and ONECUT3, were identified and might play crucial roles in the molecular pathogenesis of periodontitis. Additionally, a miRNA-mRNA-TF coregulatory network was established.ConclusionIn this study, we performed an integrated analysis based on public databases to identify specific TFs, miRNAs, and mRNAs that may play a pivotal role in periodontitis. On this basis, a TF-miRNA-mRNA network was established to provide a comprehensive perspective of the regulatory mechanism networks of periodontitis.
| S-EPMC8994180 | biostudies-literature
Project description:The regulation of gene expression in cells, including by microRNAs (miRNAs), is a dynamic process. Current methods for identifying miRNA targets by combining sequence and miRNA and mRNA expression data do not adequately use the temporal information and thus miss important miRNAs and their targets. We developed the MIRna Dynamic Regulatory Events Miner (mirDREM), a probabilistic modeling method that uses input-output hidden Markov models to reconstruct dynamic regulatory networks that explain how temporal gene expression is jointly regulated by miRNAs and transcription factors. We measured miRNA and mRNA expression for postnatal lung development in mice and used mirDREM to study the regulation of this process. The reconstructed dynamic network correctly identified known miRNAs and transcription factors. The method has also provided predictions about additional miRNAs regulating this process and the specific developmental phases they regulate, several of which were experimentally validated. Our analysis uncovered links between miRNAs involved in lung development and differentially expressed miRNAs in idiopathic pulmonary fibrosis patients, some of which we have experimentally validated using proliferation assays. These results indicate that some disease progression pathways in idiopathic pulmonary fibrosis may represent partial reversal of lung differentiation.
| S-EPMC3785769 | biostudies-literature
Project description:MicroRNAs (miRNAs) and fibroblast growth factor (FGF) signaling regulate a wide range of cellular functions, including cell specification, proliferation, migration, differentiation, and survival. In lens, both these systems control lens fiber cell differentiation; however, a possible link between these processes remains to be examined. Herein, the functional requirement for miRNAs in differentiating lens fiber cells was demonstrated via conditional inactivation of Dicer1 in mouse (Mus musculus) lens. To dissect the miRNA-dependent pathways during lens differentiation, we used a rat (Rattus norvegicus) lens epithelial explant system, induced by FGF2 to differentiate, followed by mRNA and miRNA expression profiling. Transcriptome and miRNome analysis identified extensive FGF2-regulated cellular responses that were both independent and dependent on miRNAs. We identified 131 FGF2-regulated miRNAs. Seventy-six of these miRNAs had at least two in silico predicted and inversely regulated target mRNAs. Genes modulated by the greatest number of FGF-regulated miRNAs include DNA-binding transcription factors Nfib, Nfat5/OREBP, c-Maf, Ets1, and N-Myc. Activated FGF signaling influenced bone morphogenetic factor/transforming growth factor-?, Notch, and Wnt signaling cascades implicated earlier in lens differentiation. Specific miRNA:mRNA interaction networks were predicted for c-Maf, N-Myc, and Nfib (DNA-binding transcription factors); Cnot6, Cpsf6, Dicer1, and Tnrc6b (RNA to miRNA processing); and Ash1l, Med1/PBP, and Kdm5b/Jarid1b/Plu1 (chromatin remodeling). Three miRNAs, including miR-143, miR-155, and miR-301a, down-regulated expression of c-Maf in the 3'-UTR luciferase reporter assays. These present studies demonstrate for the first time global impact of activated FGF signaling in lens cell culture system and predicted novel gene regulatory networks connected by multiple miRNAs that regulate lens differentiation.
| S-EPMC3852386 | biostudies-literature