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Keywords {🔍}

mirnas, expression, pubmed, mirna, luminal, human, cancer, article, cell, mammary, google, scholar, breast, mouse, cas, epithelial, cells, mascbasal, subsets, analysis, expressed, central, microrna, stem, progenitor, genes, table, data, gene, additional, mature, hkme, target, fig, file, differentially, subset, signatures, targets, differential, epigenetic, differentiation, profiles, subpopulations, subtypes, mrna, log, normal, fold, mira,

Topics {✒️}

masc/basal-specific mirs-34b/ masc/basal-specific mirnas mir-34b mir-200b-200a-429 cluster resulted chip-seq log2 fold masc/basal-specific mirnas tend conserved luminal-specific mir-200b full size image high throughput rt-pcr anti-apoptotic protein bcl2 y-axes show fragments article download pdf breast cancer stem-cell double-negative feedback loop multi-dimensional scaling plots luminal-specific mir-34a primate-specific microrna cluster masc/basal-specific mirnas mir-1 putative transcriptional start-site primate-specific mirna cluster log2 fold change cell–cell interaction pathways multifactor rna-seq experiments utilized chip-seq data luminal-specific mirnas tend pro-survival gene mcl-1 predicts mirna-binding sites promote epithelial-mesenchymal transition targeting met/snail signaling masc/basal mirna signature luminal cell-specific mirnas large-scale mirna profiling target lineage-specific mrnas human masc/basal population including mir-10a ezh2-deficient cellular subsets results lineage-specific expression asselin-labat ml rt-pcr expression data her2/neu receptor status luminal cell-fate commitment highlighted lineage-specific mirnas de primate-specific mirnas potential mirna–mrna networks masc/basal-specific mirnas mammary stem cell embryonic stem cells stem cell activity cell stem cell mammary stem cells taqman microrna array

Schema {🗺️}

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         headline:Integration of microRNA signatures of distinct mammary epithelial cell types with their gene expression and epigenetic portraits
         description:MicroRNAs (miRNAs) have been implicated in governing lineage specification and differentiation in multiple organs; however, little is known about their specific roles in mammopoiesis. We have determined the global miRNA expression profiles of functionally distinct epithelial subpopulations in mouse and human mammary tissue, and compared these to their cognate transcriptomes and epigenomes. Finally, the human miRNA signatures were used to interrogate the different subtypes of breast cancer, with a view to determining miRNA networks deregulated during oncogenesis. RNA from sorted mouse and human mammary cell subpopulations was subjected to miRNA expression analysis using the TaqMan MicroRNA Array. Differentially expressed (DE) miRNAs were correlated with gene expression and histone methylation profiles. Analysis of miRNA signatures of the intrinsic subtypes of breast cancer in The Cancer Genome Atlas (TCGA) database versus those of normal human epithelial subpopulations was performed. Unique miRNA signatures characterized each subset (mammary stem cell (MaSC)/basal, luminal progenitor, mature luminal, stromal), with a high degree of conservation across species. Comparison of miRNA and transcriptome profiles for the epithelial subtypes revealed an inverse relationship and pinpointed key developmental genes. Interestingly, expression of the primate-specific miRNA cluster (19q13.4) was found to be restricted to the MaSC/basal subset. Comparative analysis of miRNA signatures with H3 lysine modification maps of the different epithelial subsets revealed a tight correlation between active or repressive marks for the top DE miRNAs, including derepression of miRNAs in Ezh2-deficient cellular subsets. Interrogation of TCGA-identified miRNA profiles with the miRNA signatures of different human subsets revealed specific relationships. The derivation of global miRNA expression profiles for the different mammary subpopulations provides a comprehensive resource for understanding the interplay between miRNA networks and target gene expression. These data have highlighted lineage-specific miRNAs and potential miRNA–mRNA networks, some of which are disrupted in neoplasia. Furthermore, our findings suggest that key developmental miRNAs are regulated by global changes in histone modification, thus linking the mammary epigenome with genome-wide changes in the expression of genes and miRNAs. Comparative miRNA signature analyses between normal breast epithelial cells and breast tumors confirmed an important linkage between luminal progenitor cells and basal-like tumors.
         datePublished:2015-06-18T00:00:00Z
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            Differentially Express
            Log2 Fold Change
            Mammary Stem Cell
            miRNA Signature
            Luminal Progenitor
            Cancer Research
            Oncology
            Surgical Oncology
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      headline:Integration of microRNA signatures of distinct mammary epithelial cell types with their gene expression and epigenetic portraits
      description:MicroRNAs (miRNAs) have been implicated in governing lineage specification and differentiation in multiple organs; however, little is known about their specific roles in mammopoiesis. We have determined the global miRNA expression profiles of functionally distinct epithelial subpopulations in mouse and human mammary tissue, and compared these to their cognate transcriptomes and epigenomes. Finally, the human miRNA signatures were used to interrogate the different subtypes of breast cancer, with a view to determining miRNA networks deregulated during oncogenesis. RNA from sorted mouse and human mammary cell subpopulations was subjected to miRNA expression analysis using the TaqMan MicroRNA Array. Differentially expressed (DE) miRNAs were correlated with gene expression and histone methylation profiles. Analysis of miRNA signatures of the intrinsic subtypes of breast cancer in The Cancer Genome Atlas (TCGA) database versus those of normal human epithelial subpopulations was performed. Unique miRNA signatures characterized each subset (mammary stem cell (MaSC)/basal, luminal progenitor, mature luminal, stromal), with a high degree of conservation across species. Comparison of miRNA and transcriptome profiles for the epithelial subtypes revealed an inverse relationship and pinpointed key developmental genes. Interestingly, expression of the primate-specific miRNA cluster (19q13.4) was found to be restricted to the MaSC/basal subset. Comparative analysis of miRNA signatures with H3 lysine modification maps of the different epithelial subsets revealed a tight correlation between active or repressive marks for the top DE miRNAs, including derepression of miRNAs in Ezh2-deficient cellular subsets. Interrogation of TCGA-identified miRNA profiles with the miRNA signatures of different human subsets revealed specific relationships. The derivation of global miRNA expression profiles for the different mammary subpopulations provides a comprehensive resource for understanding the interplay between miRNA networks and target gene expression. These data have highlighted lineage-specific miRNAs and potential miRNA–mRNA networks, some of which are disrupted in neoplasia. Furthermore, our findings suggest that key developmental miRNAs are regulated by global changes in histone modification, thus linking the mammary epigenome with genome-wide changes in the expression of genes and miRNAs. Comparative miRNA signature analyses between normal breast epithelial cells and breast tumors confirmed an important linkage between luminal progenitor cells and basal-like tumors.
      datePublished:2015-06-18T00:00:00Z
      dateModified:2015-06-18T00:00:00Z
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      pageEnd:16
      license:http://creativecommons.org/licenses/by/4.0/
      sameAs:https://doi.org/10.1186/s13058-015-0585-0
      keywords:
         Differentially Express
         Log2 Fold Change
         Mammary Stem Cell
         miRNA Signature
         Luminal Progenitor
         Cancer Research
         Oncology
         Surgical Oncology
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               name:Department of Mathematics and Statistics, The University of Melbourne, Parkville, Australia
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            address:
               name:ACRF Stem Cells and Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
               type:PostalAddress
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            name:The University of Melbourne
            address:
               name:Department of Medical Biology, The University of Melbourne, Parkville, Australia
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      email:[email protected]
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      name:ACRF Stem Cells and Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
      name:Department of Medical Biology, The University of Melbourne, Parkville, Australia
      name:Department of Medical Biology, The University of Melbourne, Parkville, Australia
      name:Bioinformatics Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
      name:Centre for Cancer Biology, SA Pathology and University of South Australia, Adelaide, Australia
      name:Bioinformatics Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
      name:ACRF Stem Cells and Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
      name:Department of Medical Biology, The University of Melbourne, Parkville, Australia
      name:ACRF Stem Cells and Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
      name:Department of Medical Biology, The University of Melbourne, Parkville, Australia
      name:Bioinformatics Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
      name:Department of Computing and Information Systems, The University of Melbourne, Parkville, Australia
      name:Bioinformatics Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
      name:ACRF Stem Cells and Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
      name:Department of Medical Biology, The University of Melbourne, Parkville, Australia
      name:Centre for Cancer Biology, SA Pathology and University of South Australia, Adelaide, Australia
      name:School of Medicine and School of Molecular and Biomedical Science, University of Adelaide, Adelaide, Australia
      name:ACRF Stem Cells and Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
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      name:Bioinformatics Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
      name:Department of Mathematics and Statistics, The University of Melbourne, Parkville, Australia
      name:ACRF Stem Cells and Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
      name:Department of Medical Biology, The University of Melbourne, Parkville, Australia

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