Integration of BRCA1-mediated miRNA and mRNA profiles reveals microRNA regulation of TRAF2 and NFκB pathway View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2011-12-14

AUTHORS

Miljana Tanic, Magdalena Zajac, Gonzalo Gómez-López, Javier Benítez, Beatriz Martínez-Delgado

ABSTRACT

Microarray-based techniques are being useful to obtain miRNA and gene expression signatures associated with different tumors. BRCA1 deregulation is a frequent event in the pathogenesis of breast as well as other cancers. In addition to DNA repair functions of BRCA1, it is involved in a wide range of cellular processes such as cell cycle, chromatin remodeling or transcription. However, the molecular events underlying BRCA1-associated tumorigenesis are still largely unknown. In order to deepen our understanding of BRCA1-associated tumorigenesis, we integrated data from mRNA and miRNA microarray experiments on HCC1937 breast cancer cell line, and the isogenic HCC1937 stably expressing BRCA1, to obtain significant miRNA–mRNA relationships associated with the presence of BRCA1 gene. By using bioinformatic integration of gene and miRNA expression data, we found significant miRNA–gene relationships underlying the array signatures. We additionally evaluated the role of these statistically significant pairs at the biological pathways level and identified MAPK and NF-κB pathways associated with these expression changes. Furthermore, we experimentally validated miRNAs induced by BRCA1 that commonly regulate TRAF2, a key regulator of NF-κB and MAPK pathways. We demonstrate that miR-146a, miR-99b and miR-205, induced in HCC1937 BRCA1-expressing cells, bind and regulate TRAF2 gene. In addition, re-expression of miR-146a, miR-99b or miR-205 in HCC1937 BRCA1-null cells was sufficient to modulate NF-κB activity. Our results demonstrate that integration of mRNA and miRNA associated with BRCA1 expression was useful to discover new miRNA–gene interactions as molecular events underlying BRCA1-mediated tumorigenesis. More... »

PAGES

41-51

References to SciGraph publications

  • 2007-10-27. NF-κB pathway inhibitors preferentially inhibit breast cancer stem-like cells in BREAST CANCER RESEARCH AND TREATMENT
  • 2009-09-01. mRNA expression profiles show differential regulatory effects of microRNAs between estrogen receptor-positive and estrogen receptor-negative breast cancer in GENOME BIOLOGY
  • 1996-08. Transcriptional activation by BRCA1 in NATURE
  • 2005-06. MicroRNA expression profiles classify human cancers in NATURE
  • 2009-10. Causes and consequences of microRNA dysregulation in cancer in NATURE REVIEWS GENETICS
  • 2009-10-13. Gene expression profiling integrated into network modelling reveals heterogeneity in the mechanisms of BRCA1 tumorigenesis in BRITISH JOURNAL OF CANCER
  • 2010-05-20. Mantle cell lymphoma: transcriptional regulation by microRNAs in LEUKEMIA
  • 2007-10-08. MicroRNA expression profiling of human breast cancer identifies new markers of tumor subtype in GENOME BIOLOGY
  • 2009-12-23. BRCA1 and its toolbox for the maintenance of genome integrity in NATURE REVIEWS MOLECULAR CELL BIOLOGY
  • 2009-09-29. Key signalling nodes in mammary gland development and cancer. Mitogen-activated protein kinase signalling in experimental models of breast cancer progression and in mammary gland development in BREAST CANCER RESEARCH
  • 1999-12-01. The pathology of familial breast cancer: The pathology of familial breast cancer How do the functions of BRCA1 and BRCA2 relate to breast tumour pathology? in BREAST CANCER RESEARCH
  • 2008-05-26. Expression of microRNA-146 suppresses NF-κB activity with reduction of metastatic potential in breast cancer cells in ONCOGENE
  • 2006-10-02. BRCA1 dysfunction in sporadic basal-like breast cancer in ONCOGENE
  • 2002-08-26. BRCA1 induces DNA damage recognition factors and enhances nucleotide excision repair in NATURE GENETICS
  • 2007-10-12. Estrogen receptor α, BRCA1, and FANCF promoter methylation occur in distinct subsets of sporadic breast cancers in BREAST CANCER RESEARCH AND TREATMENT
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1007/s10549-011-1905-4

    DOI

    http://dx.doi.org/10.1007/s10549-011-1905-4

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1035530194

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/22167321


    Indexing Status Check whether this publication has been indexed by Scopus and Web Of Science using the SN Indexing Status Tool
    Incoming Citations Browse incoming citations for this publication using opencitations.net

    JSON-LD is the canonical representation for SciGraph data.

    TIP: You can open this SciGraph record using an external JSON-LD service: JSON-LD Playground Google SDTT

    [
      {
        "@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json", 
        "about": [
          {
            "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/11", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Medical and Health Sciences", 
            "type": "DefinedTerm"
          }, 
          {
            "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/1103", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Clinical Sciences", 
            "type": "DefinedTerm"
          }, 
          {
            "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/1112", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Oncology and Carcinogenesis", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "BRCA1 Protein", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Base Sequence", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Breast Neoplasms", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Cell Line, Tumor", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Cell Proliferation", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Female", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Gene Expression Regulation, Neoplastic", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Gene Regulatory Networks", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Genes, Reporter", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Humans", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Luciferases, Firefly", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "MicroRNAs", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Mitogen-Activated Protein Kinases", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "NF-kappa B", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Oligonucleotide Array Sequence Analysis", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "RNA Interference", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "RNA, Messenger", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Signal Transduction", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "TNF Receptor-Associated Factor 2", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Transcriptome", 
            "type": "DefinedTerm"
          }
        ], 
        "author": [
          {
            "affiliation": {
              "alternateName": "Human Genetics Group, Spanish National Cancer Research Centre (CNIO), Melchor Fernandez Almagro 3, 28029, Madrid, Spain", 
              "id": "http://www.grid.ac/institutes/grid.7719.8", 
              "name": [
                "Human Genetics Group, Spanish National Cancer Research Centre (CNIO), Melchor Fernandez Almagro 3, 28029, Madrid, Spain"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Tanic", 
            "givenName": "Miljana", 
            "id": "sg:person.0751706321.54", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0751706321.54"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Human Genetics Group, Spanish National Cancer Research Centre (CNIO), Melchor Fernandez Almagro 3, 28029, Madrid, Spain", 
              "id": "http://www.grid.ac/institutes/grid.7719.8", 
              "name": [
                "Human Genetics Group, Spanish National Cancer Research Centre (CNIO), Melchor Fernandez Almagro 3, 28029, Madrid, Spain"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Zajac", 
            "givenName": "Magdalena", 
            "id": "sg:person.01271062453.22", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01271062453.22"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Bioinformatics Unit, Spanish National Cancer Research Centre (CNIO), Madrid, Spain", 
              "id": "http://www.grid.ac/institutes/grid.7719.8", 
              "name": [
                "Bioinformatics Unit, Spanish National Cancer Research Centre (CNIO), Madrid, Spain"
              ], 
              "type": "Organization"
            }, 
            "familyName": "G\u00f3mez-L\u00f3pez", 
            "givenName": "Gonzalo", 
            "id": "sg:person.0700636421.39", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0700636421.39"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), (CNIO), Madrid, Spain", 
              "id": "http://www.grid.ac/institutes/grid.452372.5", 
              "name": [
                "Human Genetics Group, Spanish National Cancer Research Centre (CNIO), Melchor Fernandez Almagro 3, 28029, Madrid, Spain", 
                "Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), (CNIO), Madrid, Spain"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Ben\u00edtez", 
            "givenName": "Javier", 
            "id": "sg:person.01333446703.24", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01333446703.24"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), (CNIO), Madrid, Spain", 
              "id": "http://www.grid.ac/institutes/grid.452372.5", 
              "name": [
                "Human Genetics Group, Spanish National Cancer Research Centre (CNIO), Melchor Fernandez Almagro 3, 28029, Madrid, Spain", 
                "Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), (CNIO), Madrid, Spain"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Mart\u00ednez-Delgado", 
            "givenName": "Beatriz", 
            "id": "sg:person.0724321734.42", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0724321734.42"
            ], 
            "type": "Person"
          }
        ], 
        "citation": [
          {
            "id": "sg:pub.10.1186/gb-2009-10-9-r90", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1009104686", 
              "https://doi.org/10.1186/gb-2009-10-9-r90"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/leu.2010.91", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1028617507", 
              "https://doi.org/10.1038/leu.2010.91"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/sj.onc.1210014", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1039037705", 
              "https://doi.org/10.1038/sj.onc.1210014"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nature03702", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1024825726", 
              "https://doi.org/10.1038/nature03702"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/ng953", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1051487013", 
              "https://doi.org/10.1038/ng953"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1186/bcr12", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1031691900", 
              "https://doi.org/10.1186/bcr12"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nrm2831", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1016970769", 
              "https://doi.org/10.1038/nrm2831"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s10549-007-9766-6", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1033424786", 
              "https://doi.org/10.1007/s10549-007-9766-6"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nrg2634", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1040605557", 
              "https://doi.org/10.1038/nrg2634"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s10549-007-9798-y", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1046109199", 
              "https://doi.org/10.1007/s10549-007-9798-y"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1186/bcr2361", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1040461259", 
              "https://doi.org/10.1186/bcr2361"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/sj.bjc.6605275", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1032501067", 
              "https://doi.org/10.1038/sj.bjc.6605275"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/onc.2008.171", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1046998641", 
              "https://doi.org/10.1038/onc.2008.171"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/382678a0", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1002606918", 
              "https://doi.org/10.1038/382678a0"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1186/gb-2007-8-10-r214", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1008503544", 
              "https://doi.org/10.1186/gb-2007-8-10-r214"
            ], 
            "type": "CreativeWork"
          }
        ], 
        "datePublished": "2011-12-14", 
        "datePublishedReg": "2011-12-14", 
        "description": "Microarray-based techniques are being useful to obtain miRNA and gene expression signatures associated with different tumors. BRCA1 deregulation is a frequent event in the pathogenesis of breast as well as other cancers. In addition to DNA repair functions of BRCA1, it is involved in a wide range of cellular processes such as cell cycle, chromatin remodeling or transcription. However, the molecular events underlying BRCA1-associated tumorigenesis are still largely unknown. In order to deepen our understanding of BRCA1-associated tumorigenesis, we integrated data from mRNA and miRNA microarray experiments on HCC1937 breast cancer cell line, and the isogenic HCC1937 stably expressing BRCA1, to obtain significant miRNA\u2013mRNA relationships associated with the presence of BRCA1 gene. By using bioinformatic integration of gene and miRNA expression data, we found significant miRNA\u2013gene relationships underlying the array signatures. We additionally evaluated the role of these statistically significant pairs at the biological pathways level and identified MAPK and NF-\u03baB pathways associated with these expression changes. Furthermore, we experimentally validated miRNAs induced by BRCA1 that commonly regulate TRAF2, a key regulator of NF-\u03baB and MAPK pathways. We demonstrate that miR-146a, miR-99b and miR-205, induced in HCC1937 BRCA1-expressing cells, bind and regulate TRAF2 gene. In addition, re-expression of miR-146a, miR-99b or miR-205 in HCC1937 BRCA1-null cells was sufficient to modulate NF-\u03baB activity. Our results demonstrate that integration of mRNA and miRNA associated with BRCA1 expression was useful to discover new miRNA\u2013gene interactions as molecular events underlying BRCA1-mediated tumorigenesis.", 
        "genre": "article", 
        "id": "sg:pub.10.1007/s10549-011-1905-4", 
        "inLanguage": "en", 
        "isAccessibleForFree": false, 
        "isPartOf": [
          {
            "id": "sg:journal.1092777", 
            "issn": [
              "0167-6806", 
              "1573-7217"
            ], 
            "name": "Breast Cancer Research and Treatment", 
            "publisher": "Springer Nature", 
            "type": "Periodical"
          }, 
          {
            "issueNumber": "1", 
            "type": "PublicationIssue"
          }, 
          {
            "type": "PublicationVolume", 
            "volumeNumber": "134"
          }
        ], 
        "keywords": [
          "miRNA-gene interactions", 
          "molecular events", 
          "integration of mRNA", 
          "DNA repair function", 
          "biological pathway level", 
          "regulation of TRAF2", 
          "BRCA1-associated tumorigenesis", 
          "miRNA expression data", 
          "chromatin remodeling", 
          "BRCA1-null cells", 
          "pathogenesis of breast", 
          "gene expression signatures", 
          "cellular processes", 
          "bioinformatic integration", 
          "mRNA relationships", 
          "repair function", 
          "expression changes", 
          "key regulator", 
          "cell cycle", 
          "MAPK pathway", 
          "pathway level", 
          "expression data", 
          "TRAF2 gene", 
          "miRNA", 
          "expression signatures", 
          "genes", 
          "NF-\u03baB activity", 
          "BRCA1 expression", 
          "NF-\u03baB pathway", 
          "NF-\u03baB", 
          "cancer cell lines", 
          "tumorigenesis", 
          "TRAF2", 
          "cell lines", 
          "mRNA", 
          "pathway", 
          "NF\u03baB pathway", 
          "breast cancer cell lines", 
          "BRCA1 gene", 
          "miR-99b", 
          "BRCA1", 
          "frequent event", 
          "miR-205", 
          "significant pairs", 
          "cells", 
          "transcription", 
          "miRNAs", 
          "MAPK", 
          "miR-146a", 
          "regulator", 
          "microarrays", 
          "binds", 
          "regulation", 
          "different tumors", 
          "deregulation", 
          "HCC1937", 
          "expression", 
          "remodeling", 
          "signatures", 
          "events", 
          "wide range", 
          "array signature", 
          "role", 
          "activity", 
          "addition", 
          "lines", 
          "interaction", 
          "cycle", 
          "pathogenesis", 
          "function", 
          "understanding", 
          "pairs", 
          "presence", 
          "relationship", 
          "cancer", 
          "levels", 
          "changes", 
          "integration", 
          "data", 
          "process", 
          "experiments", 
          "tumors", 
          "range", 
          "results", 
          "order", 
          "breast", 
          "technique", 
          "BRCA1 deregulation", 
          "HCC1937 breast cancer cell line", 
          "isogenic HCC1937", 
          "significant miRNA\u2013gene relationships", 
          "miRNA\u2013gene relationships", 
          "HCC1937 BRCA1-expressing cells", 
          "BRCA1-expressing cells", 
          "HCC1937 BRCA1-null cells", 
          "new miRNA\u2013gene interactions", 
          "BRCA1-mediated tumorigenesis", 
          "BRCA1-mediated miRNA"
        ], 
        "name": "Integration of BRCA1-mediated miRNA and mRNA profiles reveals microRNA regulation of TRAF2 and NF\u03baB pathway", 
        "pagination": "41-51", 
        "productId": [
          {
            "name": "dimensions_id", 
            "type": "PropertyValue", 
            "value": [
              "pub.1035530194"
            ]
          }, 
          {
            "name": "doi", 
            "type": "PropertyValue", 
            "value": [
              "10.1007/s10549-011-1905-4"
            ]
          }, 
          {
            "name": "pubmed_id", 
            "type": "PropertyValue", 
            "value": [
              "22167321"
            ]
          }
        ], 
        "sameAs": [
          "https://doi.org/10.1007/s10549-011-1905-4", 
          "https://app.dimensions.ai/details/publication/pub.1035530194"
        ], 
        "sdDataset": "articles", 
        "sdDatePublished": "2021-11-01T18:16", 
        "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
        "sdPublisher": {
          "name": "Springer Nature - SN SciGraph project", 
          "type": "Organization"
        }, 
        "sdSource": "s3://com-springernature-scigraph/baseset/20211101/entities/gbq_results/article/article_541.jsonl", 
        "type": "ScholarlyArticle", 
        "url": "https://doi.org/10.1007/s10549-011-1905-4"
      }
    ]
     

    Download the RDF metadata as:  json-ld nt turtle xml License info

    HOW TO GET THIS DATA PROGRAMMATICALLY:

    JSON-LD is a popular format for linked data which is fully compatible with JSON.

    curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1007/s10549-011-1905-4'

    N-Triples is a line-based linked data format ideal for batch operations.

    curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1007/s10549-011-1905-4'

    Turtle is a human-readable linked data format.

    curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1007/s10549-011-1905-4'

    RDF/XML is a standard XML format for linked data.

    curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1007/s10549-011-1905-4'


     

    This table displays all metadata directly associated to this object as RDF triples.

    338 TRIPLES      22 PREDICATES      160 URIs      136 LITERALS      27 BLANK NODES

    Subject Predicate Object
    1 sg:pub.10.1007/s10549-011-1905-4 schema:about N021e7fcceb3c4e1db0d3652eb88f0c98
    2 N06914a2592c74f9280f87a2d5936307e
    3 N4b9ed67166b443799061475f28c4aca1
    4 N528c67b363ea49bfb938fe307392013d
    5 N5c626d959b8a4ec1b7500bd68fe36c5d
    6 N71031fc396204d0c8ce9eab1ed29e3eb
    7 N7c304236e1f346b79318e9a984b54015
    8 N818b4aecc6f94eafaac07edd026e7927
    9 N9d3411353227455490def19d9095de53
    10 Na239fdeb001548faa01e2ff177462a03
    11 Na2f2eba5763449739edcb00f6324dee7
    12 Nb6e420c6ff3c468786326f2f3d0bbdc1
    13 Nbef46aab708d454d893dae3c444d35e3
    14 Ncbcabb7b96fb42b89501efa9c39d851a
    15 Nce49fc2967e346ff921ee29a1635df9f
    16 Ncf38ae4b59ff402181911efd45e98c73
    17 Nda7486368ee149efb110386bd34a2108
    18 Ndcd598a50c904b04ba058750f3dc008b
    19 Ne4c9c1d5379344ada12c6deeb757b7a5
    20 Nf79248e365804765b460e8cb8a999d7c
    21 anzsrc-for:11
    22 anzsrc-for:1103
    23 anzsrc-for:1112
    24 schema:author N1f9517c4a9e34e52b7a0c980f34787a4
    25 schema:citation sg:pub.10.1007/s10549-007-9766-6
    26 sg:pub.10.1007/s10549-007-9798-y
    27 sg:pub.10.1038/382678a0
    28 sg:pub.10.1038/leu.2010.91
    29 sg:pub.10.1038/nature03702
    30 sg:pub.10.1038/ng953
    31 sg:pub.10.1038/nrg2634
    32 sg:pub.10.1038/nrm2831
    33 sg:pub.10.1038/onc.2008.171
    34 sg:pub.10.1038/sj.bjc.6605275
    35 sg:pub.10.1038/sj.onc.1210014
    36 sg:pub.10.1186/bcr12
    37 sg:pub.10.1186/bcr2361
    38 sg:pub.10.1186/gb-2007-8-10-r214
    39 sg:pub.10.1186/gb-2009-10-9-r90
    40 schema:datePublished 2011-12-14
    41 schema:datePublishedReg 2011-12-14
    42 schema:description Microarray-based techniques are being useful to obtain miRNA and gene expression signatures associated with different tumors. BRCA1 deregulation is a frequent event in the pathogenesis of breast as well as other cancers. In addition to DNA repair functions of BRCA1, it is involved in a wide range of cellular processes such as cell cycle, chromatin remodeling or transcription. However, the molecular events underlying BRCA1-associated tumorigenesis are still largely unknown. In order to deepen our understanding of BRCA1-associated tumorigenesis, we integrated data from mRNA and miRNA microarray experiments on HCC1937 breast cancer cell line, and the isogenic HCC1937 stably expressing BRCA1, to obtain significant miRNA–mRNA relationships associated with the presence of BRCA1 gene. By using bioinformatic integration of gene and miRNA expression data, we found significant miRNA–gene relationships underlying the array signatures. We additionally evaluated the role of these statistically significant pairs at the biological pathways level and identified MAPK and NF-κB pathways associated with these expression changes. Furthermore, we experimentally validated miRNAs induced by BRCA1 that commonly regulate TRAF2, a key regulator of NF-κB and MAPK pathways. We demonstrate that miR-146a, miR-99b and miR-205, induced in HCC1937 BRCA1-expressing cells, bind and regulate TRAF2 gene. In addition, re-expression of miR-146a, miR-99b or miR-205 in HCC1937 BRCA1-null cells was sufficient to modulate NF-κB activity. Our results demonstrate that integration of mRNA and miRNA associated with BRCA1 expression was useful to discover new miRNA–gene interactions as molecular events underlying BRCA1-mediated tumorigenesis.
    43 schema:genre article
    44 schema:inLanguage en
    45 schema:isAccessibleForFree false
    46 schema:isPartOf N2248036de91644d4b3a9e8eddaa01a05
    47 Nfefb3078f59044c39f2500502f81de35
    48 sg:journal.1092777
    49 schema:keywords BRCA1
    50 BRCA1 deregulation
    51 BRCA1 expression
    52 BRCA1 gene
    53 BRCA1-associated tumorigenesis
    54 BRCA1-expressing cells
    55 BRCA1-mediated miRNA
    56 BRCA1-mediated tumorigenesis
    57 BRCA1-null cells
    58 DNA repair function
    59 HCC1937
    60 HCC1937 BRCA1-expressing cells
    61 HCC1937 BRCA1-null cells
    62 HCC1937 breast cancer cell line
    63 MAPK
    64 MAPK pathway
    65 NF-κB
    66 NF-κB activity
    67 NF-κB pathway
    68 NFκB pathway
    69 TRAF2
    70 TRAF2 gene
    71 activity
    72 addition
    73 array signature
    74 binds
    75 bioinformatic integration
    76 biological pathway level
    77 breast
    78 breast cancer cell lines
    79 cancer
    80 cancer cell lines
    81 cell cycle
    82 cell lines
    83 cells
    84 cellular processes
    85 changes
    86 chromatin remodeling
    87 cycle
    88 data
    89 deregulation
    90 different tumors
    91 events
    92 experiments
    93 expression
    94 expression changes
    95 expression data
    96 expression signatures
    97 frequent event
    98 function
    99 gene expression signatures
    100 genes
    101 integration
    102 integration of mRNA
    103 interaction
    104 isogenic HCC1937
    105 key regulator
    106 levels
    107 lines
    108 mRNA
    109 mRNA relationships
    110 miR-146a
    111 miR-205
    112 miR-99b
    113 miRNA
    114 miRNA expression data
    115 miRNA-gene interactions
    116 miRNAs
    117 miRNA–gene relationships
    118 microarrays
    119 molecular events
    120 new miRNA–gene interactions
    121 order
    122 pairs
    123 pathogenesis
    124 pathogenesis of breast
    125 pathway
    126 pathway level
    127 presence
    128 process
    129 range
    130 regulation
    131 regulation of TRAF2
    132 regulator
    133 relationship
    134 remodeling
    135 repair function
    136 results
    137 role
    138 signatures
    139 significant miRNA–gene relationships
    140 significant pairs
    141 technique
    142 transcription
    143 tumorigenesis
    144 tumors
    145 understanding
    146 wide range
    147 schema:name Integration of BRCA1-mediated miRNA and mRNA profiles reveals microRNA regulation of TRAF2 and NFκB pathway
    148 schema:pagination 41-51
    149 schema:productId N3db7b9a94ea742b6bd716f843bfbcc14
    150 N46f72cf018614763aa676e22d9b1977c
    151 Nb4f86addf07c45d89341e5982386d80c
    152 schema:sameAs https://app.dimensions.ai/details/publication/pub.1035530194
    153 https://doi.org/10.1007/s10549-011-1905-4
    154 schema:sdDatePublished 2021-11-01T18:16
    155 schema:sdLicense https://scigraph.springernature.com/explorer/license/
    156 schema:sdPublisher N1f48644ee040434a8db940927e3eb57e
    157 schema:url https://doi.org/10.1007/s10549-011-1905-4
    158 sgo:license sg:explorer/license/
    159 sgo:sdDataset articles
    160 rdf:type schema:ScholarlyArticle
    161 N021e7fcceb3c4e1db0d3652eb88f0c98 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    162 schema:name MicroRNAs
    163 rdf:type schema:DefinedTerm
    164 N06914a2592c74f9280f87a2d5936307e schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    165 schema:name Signal Transduction
    166 rdf:type schema:DefinedTerm
    167 N1f48644ee040434a8db940927e3eb57e schema:name Springer Nature - SN SciGraph project
    168 rdf:type schema:Organization
    169 N1f9517c4a9e34e52b7a0c980f34787a4 rdf:first sg:person.0751706321.54
    170 rdf:rest Nbbac582025af4124a9746dcb20689ce5
    171 N2248036de91644d4b3a9e8eddaa01a05 schema:volumeNumber 134
    172 rdf:type schema:PublicationVolume
    173 N3db7b9a94ea742b6bd716f843bfbcc14 schema:name pubmed_id
    174 schema:value 22167321
    175 rdf:type schema:PropertyValue
    176 N46f72cf018614763aa676e22d9b1977c schema:name doi
    177 schema:value 10.1007/s10549-011-1905-4
    178 rdf:type schema:PropertyValue
    179 N4b9ed67166b443799061475f28c4aca1 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    180 schema:name Gene Expression Regulation, Neoplastic
    181 rdf:type schema:DefinedTerm
    182 N528c67b363ea49bfb938fe307392013d schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    183 schema:name TNF Receptor-Associated Factor 2
    184 rdf:type schema:DefinedTerm
    185 N5c626d959b8a4ec1b7500bd68fe36c5d schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    186 schema:name NF-kappa B
    187 rdf:type schema:DefinedTerm
    188 N71031fc396204d0c8ce9eab1ed29e3eb schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    189 schema:name Transcriptome
    190 rdf:type schema:DefinedTerm
    191 N7c304236e1f346b79318e9a984b54015 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    192 schema:name Luciferases, Firefly
    193 rdf:type schema:DefinedTerm
    194 N7c867c66d9a84b979413e3125e3ff834 rdf:first sg:person.0700636421.39
    195 rdf:rest Nf92350aaab9f47299bd668d5c190b86b
    196 N818b4aecc6f94eafaac07edd026e7927 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    197 schema:name Gene Regulatory Networks
    198 rdf:type schema:DefinedTerm
    199 N9d3411353227455490def19d9095de53 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    200 schema:name RNA, Messenger
    201 rdf:type schema:DefinedTerm
    202 Na239fdeb001548faa01e2ff177462a03 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    203 schema:name BRCA1 Protein
    204 rdf:type schema:DefinedTerm
    205 Na2f2eba5763449739edcb00f6324dee7 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    206 schema:name Humans
    207 rdf:type schema:DefinedTerm
    208 Nb4f86addf07c45d89341e5982386d80c schema:name dimensions_id
    209 schema:value pub.1035530194
    210 rdf:type schema:PropertyValue
    211 Nb6e420c6ff3c468786326f2f3d0bbdc1 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    212 schema:name RNA Interference
    213 rdf:type schema:DefinedTerm
    214 Nbbac582025af4124a9746dcb20689ce5 rdf:first sg:person.01271062453.22
    215 rdf:rest N7c867c66d9a84b979413e3125e3ff834
    216 Nbdfa19c86c1343568e9e20fab71ff80d rdf:first sg:person.0724321734.42
    217 rdf:rest rdf:nil
    218 Nbef46aab708d454d893dae3c444d35e3 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    219 schema:name Breast Neoplasms
    220 rdf:type schema:DefinedTerm
    221 Ncbcabb7b96fb42b89501efa9c39d851a schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    222 schema:name Cell Proliferation
    223 rdf:type schema:DefinedTerm
    224 Nce49fc2967e346ff921ee29a1635df9f schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    225 schema:name Mitogen-Activated Protein Kinases
    226 rdf:type schema:DefinedTerm
    227 Ncf38ae4b59ff402181911efd45e98c73 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    228 schema:name Genes, Reporter
    229 rdf:type schema:DefinedTerm
    230 Nda7486368ee149efb110386bd34a2108 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    231 schema:name Female
    232 rdf:type schema:DefinedTerm
    233 Ndcd598a50c904b04ba058750f3dc008b schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    234 schema:name Oligonucleotide Array Sequence Analysis
    235 rdf:type schema:DefinedTerm
    236 Ne4c9c1d5379344ada12c6deeb757b7a5 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    237 schema:name Cell Line, Tumor
    238 rdf:type schema:DefinedTerm
    239 Nf79248e365804765b460e8cb8a999d7c schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    240 schema:name Base Sequence
    241 rdf:type schema:DefinedTerm
    242 Nf92350aaab9f47299bd668d5c190b86b rdf:first sg:person.01333446703.24
    243 rdf:rest Nbdfa19c86c1343568e9e20fab71ff80d
    244 Nfefb3078f59044c39f2500502f81de35 schema:issueNumber 1
    245 rdf:type schema:PublicationIssue
    246 anzsrc-for:11 schema:inDefinedTermSet anzsrc-for:
    247 schema:name Medical and Health Sciences
    248 rdf:type schema:DefinedTerm
    249 anzsrc-for:1103 schema:inDefinedTermSet anzsrc-for:
    250 schema:name Clinical Sciences
    251 rdf:type schema:DefinedTerm
    252 anzsrc-for:1112 schema:inDefinedTermSet anzsrc-for:
    253 schema:name Oncology and Carcinogenesis
    254 rdf:type schema:DefinedTerm
    255 sg:journal.1092777 schema:issn 0167-6806
    256 1573-7217
    257 schema:name Breast Cancer Research and Treatment
    258 schema:publisher Springer Nature
    259 rdf:type schema:Periodical
    260 sg:person.01271062453.22 schema:affiliation grid-institutes:grid.7719.8
    261 schema:familyName Zajac
    262 schema:givenName Magdalena
    263 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01271062453.22
    264 rdf:type schema:Person
    265 sg:person.01333446703.24 schema:affiliation grid-institutes:grid.452372.5
    266 schema:familyName Benítez
    267 schema:givenName Javier
    268 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01333446703.24
    269 rdf:type schema:Person
    270 sg:person.0700636421.39 schema:affiliation grid-institutes:grid.7719.8
    271 schema:familyName Gómez-López
    272 schema:givenName Gonzalo
    273 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0700636421.39
    274 rdf:type schema:Person
    275 sg:person.0724321734.42 schema:affiliation grid-institutes:grid.452372.5
    276 schema:familyName Martínez-Delgado
    277 schema:givenName Beatriz
    278 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0724321734.42
    279 rdf:type schema:Person
    280 sg:person.0751706321.54 schema:affiliation grid-institutes:grid.7719.8
    281 schema:familyName Tanic
    282 schema:givenName Miljana
    283 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0751706321.54
    284 rdf:type schema:Person
    285 sg:pub.10.1007/s10549-007-9766-6 schema:sameAs https://app.dimensions.ai/details/publication/pub.1033424786
    286 https://doi.org/10.1007/s10549-007-9766-6
    287 rdf:type schema:CreativeWork
    288 sg:pub.10.1007/s10549-007-9798-y schema:sameAs https://app.dimensions.ai/details/publication/pub.1046109199
    289 https://doi.org/10.1007/s10549-007-9798-y
    290 rdf:type schema:CreativeWork
    291 sg:pub.10.1038/382678a0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1002606918
    292 https://doi.org/10.1038/382678a0
    293 rdf:type schema:CreativeWork
    294 sg:pub.10.1038/leu.2010.91 schema:sameAs https://app.dimensions.ai/details/publication/pub.1028617507
    295 https://doi.org/10.1038/leu.2010.91
    296 rdf:type schema:CreativeWork
    297 sg:pub.10.1038/nature03702 schema:sameAs https://app.dimensions.ai/details/publication/pub.1024825726
    298 https://doi.org/10.1038/nature03702
    299 rdf:type schema:CreativeWork
    300 sg:pub.10.1038/ng953 schema:sameAs https://app.dimensions.ai/details/publication/pub.1051487013
    301 https://doi.org/10.1038/ng953
    302 rdf:type schema:CreativeWork
    303 sg:pub.10.1038/nrg2634 schema:sameAs https://app.dimensions.ai/details/publication/pub.1040605557
    304 https://doi.org/10.1038/nrg2634
    305 rdf:type schema:CreativeWork
    306 sg:pub.10.1038/nrm2831 schema:sameAs https://app.dimensions.ai/details/publication/pub.1016970769
    307 https://doi.org/10.1038/nrm2831
    308 rdf:type schema:CreativeWork
    309 sg:pub.10.1038/onc.2008.171 schema:sameAs https://app.dimensions.ai/details/publication/pub.1046998641
    310 https://doi.org/10.1038/onc.2008.171
    311 rdf:type schema:CreativeWork
    312 sg:pub.10.1038/sj.bjc.6605275 schema:sameAs https://app.dimensions.ai/details/publication/pub.1032501067
    313 https://doi.org/10.1038/sj.bjc.6605275
    314 rdf:type schema:CreativeWork
    315 sg:pub.10.1038/sj.onc.1210014 schema:sameAs https://app.dimensions.ai/details/publication/pub.1039037705
    316 https://doi.org/10.1038/sj.onc.1210014
    317 rdf:type schema:CreativeWork
    318 sg:pub.10.1186/bcr12 schema:sameAs https://app.dimensions.ai/details/publication/pub.1031691900
    319 https://doi.org/10.1186/bcr12
    320 rdf:type schema:CreativeWork
    321 sg:pub.10.1186/bcr2361 schema:sameAs https://app.dimensions.ai/details/publication/pub.1040461259
    322 https://doi.org/10.1186/bcr2361
    323 rdf:type schema:CreativeWork
    324 sg:pub.10.1186/gb-2007-8-10-r214 schema:sameAs https://app.dimensions.ai/details/publication/pub.1008503544
    325 https://doi.org/10.1186/gb-2007-8-10-r214
    326 rdf:type schema:CreativeWork
    327 sg:pub.10.1186/gb-2009-10-9-r90 schema:sameAs https://app.dimensions.ai/details/publication/pub.1009104686
    328 https://doi.org/10.1186/gb-2009-10-9-r90
    329 rdf:type schema:CreativeWork
    330 grid-institutes:grid.452372.5 schema:alternateName Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), (CNIO), Madrid, Spain
    331 schema:name Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), (CNIO), Madrid, Spain
    332 Human Genetics Group, Spanish National Cancer Research Centre (CNIO), Melchor Fernandez Almagro 3, 28029, Madrid, Spain
    333 rdf:type schema:Organization
    334 grid-institutes:grid.7719.8 schema:alternateName Bioinformatics Unit, Spanish National Cancer Research Centre (CNIO), Madrid, Spain
    335 Human Genetics Group, Spanish National Cancer Research Centre (CNIO), Melchor Fernandez Almagro 3, 28029, Madrid, Spain
    336 schema:name Bioinformatics Unit, Spanish National Cancer Research Centre (CNIO), Madrid, Spain
    337 Human Genetics Group, Spanish National Cancer Research Centre (CNIO), Melchor Fernandez Almagro 3, 28029, Madrid, Spain
    338 rdf:type schema:Organization
     




    Preview window. Press ESC to close (or click here)


    ...