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

  • 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
  • 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
  • 2007-10-27. NF-κB pathway inhibitors preferentially inhibit breast cancer stem-like cells in BREAST CANCER RESEARCH AND TREATMENT
  • 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
  • 2009-10-13. Gene expression profiling integrated into network modelling reveals heterogeneity in the mechanisms of BRCA1 tumorigenesis in BRITISH JOURNAL OF CANCER
  • 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.10.1038/382678a0", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1002606918", 
              "https://doi.org/10.1038/382678a0"
            ], 
            "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/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/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.10.1186/bcr2361", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1040461259", 
              "https://doi.org/10.1186/bcr2361"
            ], 
            "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.10.1007/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/nrm2831", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1016970769", 
              "https://doi.org/10.1038/nrm2831"
            ], 
            "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.10.1186/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.10.1007/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.10.1038/nrg2634", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1040605557", 
              "https://doi.org/10.1038/nrg2634"
            ], 
            "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": "2022-01-01T18:24", 
        "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
        "sdPublisher": {
          "name": "Springer Nature - SN SciGraph project", 
          "type": "Organization"
        }, 
        "sdSource": "s3://com-springernature-scigraph/baseset/20220101/entities/gbq_results/article/article_544.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 N18a2739fdbe8497088166d0d05a39cc2
    2 N2375ee423bcf474c8abf2dfd8e7a6140
    3 N27ee91c52b1f4bb6848c1ae877a38be0
    4 N2e7599ef8cc74cc7aeac49a0aab54c1c
    5 N374b1752534b4e5b8a81bd14715477df
    6 N429d4a792fc0454b8316ab964f92b1ce
    7 N6b1a2d9d9b824d13a444d7087f195e6d
    8 N94b5428c24004b5192daf8148a3075ef
    9 Na9036fff52814bfda0349fae3381ba17
    10 Nad82ef9f391e44aaa725a08e2f62d9f0
    11 Nb0dd7c32c6ed4aa18d69250b38f3d7c6
    12 Nbc0e3421e6c74525900e84878b59d61e
    13 Nc188c5b9480e4b57af8a92617e070115
    14 Nc2271bc1f7ff4eceb2df8c938d9ba8d6
    15 Ndd0e19fb37fb4823b0538895bb97af2d
    16 Ne0f6ad2ffff344f19007555eadc41ebe
    17 Nea5615a4d12144388ea9a22202d1f370
    18 Nf666b35d8c324215a3c66e21c74a8775
    19 Nf7476cfe276a4d88bebaa7da2adaff1b
    20 Nfda1ef2559684ec782cd1dd17bce439e
    21 anzsrc-for:11
    22 anzsrc-for:1103
    23 anzsrc-for:1112
    24 schema:author N3af030634d754131bb45d4e6acdaa7c7
    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 N4aa8b7b82dd8402daf4fbcb4ef273f19
    47 N7889838ce4c44db597907f22e8986d38
    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 N38678b88d3274f99995cb34e78fbf20a
    150 N9ae6511c9776464bad729f6266a2f8ad
    151 Ncb97350c791c417b8f6e344b559de31b
    152 schema:sameAs https://app.dimensions.ai/details/publication/pub.1035530194
    153 https://doi.org/10.1007/s10549-011-1905-4
    154 schema:sdDatePublished 2022-01-01T18:24
    155 schema:sdLicense https://scigraph.springernature.com/explorer/license/
    156 schema:sdPublisher N3156193f55084fab8e15b19056a8c9b9
    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 N05e891d660d24048b3f5e8a898297524 rdf:first sg:person.0724321734.42
    162 rdf:rest rdf:nil
    163 N110b9c4208354f09a5a0ac019fd6872b rdf:first sg:person.01333446703.24
    164 rdf:rest N05e891d660d24048b3f5e8a898297524
    165 N152e7ca6bdf84759aa63fcde913c933e rdf:first sg:person.0700636421.39
    166 rdf:rest N110b9c4208354f09a5a0ac019fd6872b
    167 N18a2739fdbe8497088166d0d05a39cc2 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    168 schema:name Oligonucleotide Array Sequence Analysis
    169 rdf:type schema:DefinedTerm
    170 N2375ee423bcf474c8abf2dfd8e7a6140 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    171 schema:name Mitogen-Activated Protein Kinases
    172 rdf:type schema:DefinedTerm
    173 N27ee91c52b1f4bb6848c1ae877a38be0 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    174 schema:name Signal Transduction
    175 rdf:type schema:DefinedTerm
    176 N2e7599ef8cc74cc7aeac49a0aab54c1c schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    177 schema:name Cell Line, Tumor
    178 rdf:type schema:DefinedTerm
    179 N2f7816841970407ba5b1e8b74076c84d rdf:first sg:person.01271062453.22
    180 rdf:rest N152e7ca6bdf84759aa63fcde913c933e
    181 N3156193f55084fab8e15b19056a8c9b9 schema:name Springer Nature - SN SciGraph project
    182 rdf:type schema:Organization
    183 N374b1752534b4e5b8a81bd14715477df schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    184 schema:name Luciferases, Firefly
    185 rdf:type schema:DefinedTerm
    186 N38678b88d3274f99995cb34e78fbf20a schema:name pubmed_id
    187 schema:value 22167321
    188 rdf:type schema:PropertyValue
    189 N3af030634d754131bb45d4e6acdaa7c7 rdf:first sg:person.0751706321.54
    190 rdf:rest N2f7816841970407ba5b1e8b74076c84d
    191 N429d4a792fc0454b8316ab964f92b1ce schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    192 schema:name Gene Expression Regulation, Neoplastic
    193 rdf:type schema:DefinedTerm
    194 N4aa8b7b82dd8402daf4fbcb4ef273f19 schema:volumeNumber 134
    195 rdf:type schema:PublicationVolume
    196 N6b1a2d9d9b824d13a444d7087f195e6d schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    197 schema:name Breast Neoplasms
    198 rdf:type schema:DefinedTerm
    199 N7889838ce4c44db597907f22e8986d38 schema:issueNumber 1
    200 rdf:type schema:PublicationIssue
    201 N94b5428c24004b5192daf8148a3075ef schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    202 schema:name BRCA1 Protein
    203 rdf:type schema:DefinedTerm
    204 N9ae6511c9776464bad729f6266a2f8ad schema:name doi
    205 schema:value 10.1007/s10549-011-1905-4
    206 rdf:type schema:PropertyValue
    207 Na9036fff52814bfda0349fae3381ba17 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    208 schema:name RNA Interference
    209 rdf:type schema:DefinedTerm
    210 Nad82ef9f391e44aaa725a08e2f62d9f0 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    211 schema:name TNF Receptor-Associated Factor 2
    212 rdf:type schema:DefinedTerm
    213 Nb0dd7c32c6ed4aa18d69250b38f3d7c6 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    214 schema:name MicroRNAs
    215 rdf:type schema:DefinedTerm
    216 Nbc0e3421e6c74525900e84878b59d61e schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    217 schema:name Genes, Reporter
    218 rdf:type schema:DefinedTerm
    219 Nc188c5b9480e4b57af8a92617e070115 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    220 schema:name Transcriptome
    221 rdf:type schema:DefinedTerm
    222 Nc2271bc1f7ff4eceb2df8c938d9ba8d6 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    223 schema:name NF-kappa B
    224 rdf:type schema:DefinedTerm
    225 Ncb97350c791c417b8f6e344b559de31b schema:name dimensions_id
    226 schema:value pub.1035530194
    227 rdf:type schema:PropertyValue
    228 Ndd0e19fb37fb4823b0538895bb97af2d schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    229 schema:name Cell Proliferation
    230 rdf:type schema:DefinedTerm
    231 Ne0f6ad2ffff344f19007555eadc41ebe schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    232 schema:name Gene Regulatory Networks
    233 rdf:type schema:DefinedTerm
    234 Nea5615a4d12144388ea9a22202d1f370 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    235 schema:name Humans
    236 rdf:type schema:DefinedTerm
    237 Nf666b35d8c324215a3c66e21c74a8775 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    238 schema:name Base Sequence
    239 rdf:type schema:DefinedTerm
    240 Nf7476cfe276a4d88bebaa7da2adaff1b schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    241 schema:name RNA, Messenger
    242 rdf:type schema:DefinedTerm
    243 Nfda1ef2559684ec782cd1dd17bce439e schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    244 schema:name Female
    245 rdf:type schema:DefinedTerm
    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)


    ...