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Topics {✒️}

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WebPage:
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         headline:The human lncRNA LINC-PINT inhibits tumor cell invasion through a highly conserved sequence element
         description:It is now obvious that the majority of cellular transcripts do not code for proteins, and a significant subset of them are long non-coding RNAs (lncRNAs). Many lncRNAs show aberrant expression in cancer, and some of them have been linked to cell transformation. However, the underlying mechanisms remain poorly understood and it is unknown how the sequences of lncRNA dictate their function. Here we characterize the function of the p53-regulated human lncRNA LINC-PINT in cancer. We find that LINC-PINT is downregulated in multiple types of cancer and acts as a tumor suppressor lncRNA by reducing the invasive phenotype of cancer cells. A cross-species analysis identifies a highly conserved sequence element in LINC-PINT that is essential for its function. This sequence mediates a specific interaction with PRC2, necessary for the LINC-PINT-dependent repression of a pro-invasion signature of genes regulated by the transcription factor EGR1. Our findings support a conserved functional co-dependence between LINC-PINT and PRC2 and lead us to propose a new mechanism where the lncRNA regulates the availability of free PRC2 at the proximity of co-regulated genomic loci.
         datePublished:2017-10-27T00:00:00Z
         dateModified:2017-10-27T00:00:00Z
         pageStart:1
         pageEnd:15
         license:http://creativecommons.org/publicdomain/zero/1.0/
         sameAs:https://doi.org/10.1186/s13059-017-1331-y
         keywords:
            LncRNA
            Cancer
            Cell invasion
            Epigenetic regulation
            PRC2
            Animal Genetics and Genomics
            Human Genetics
            Plant Genetics and Genomics
            Microbial Genetics and Genomics
            Bioinformatics
            Evolutionary Biology
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      headline:The human lncRNA LINC-PINT inhibits tumor cell invasion through a highly conserved sequence element
      description:It is now obvious that the majority of cellular transcripts do not code for proteins, and a significant subset of them are long non-coding RNAs (lncRNAs). Many lncRNAs show aberrant expression in cancer, and some of them have been linked to cell transformation. However, the underlying mechanisms remain poorly understood and it is unknown how the sequences of lncRNA dictate their function. Here we characterize the function of the p53-regulated human lncRNA LINC-PINT in cancer. We find that LINC-PINT is downregulated in multiple types of cancer and acts as a tumor suppressor lncRNA by reducing the invasive phenotype of cancer cells. A cross-species analysis identifies a highly conserved sequence element in LINC-PINT that is essential for its function. This sequence mediates a specific interaction with PRC2, necessary for the LINC-PINT-dependent repression of a pro-invasion signature of genes regulated by the transcription factor EGR1. Our findings support a conserved functional co-dependence between LINC-PINT and PRC2 and lead us to propose a new mechanism where the lncRNA regulates the availability of free PRC2 at the proximity of co-regulated genomic loci.
      datePublished:2017-10-27T00:00:00Z
      dateModified:2017-10-27T00:00:00Z
      pageStart:1
      pageEnd:15
      license:http://creativecommons.org/publicdomain/zero/1.0/
      sameAs:https://doi.org/10.1186/s13059-017-1331-y
      keywords:
         LncRNA
         Cancer
         Cell invasion
         Epigenetic regulation
         PRC2
         Animal Genetics and Genomics
         Human Genetics
         Plant Genetics and Genomics
         Microbial Genetics and Genomics
         Bioinformatics
         Evolutionary Biology
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         name:BioMed Central
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      author:
            name:Oskar Marín-Béjar
            affiliation:
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                     name:Department of Gene Therapy and Regulation of Gene Expression, Center for Applied Medical Research, University of Navarra, Pamplona, Spain
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                  name:KU Leuven
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            name:Aina M. Mas
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            name:Jovanna González
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         name:Department of Gene Therapy and Regulation of Gene Expression, Center for Applied Medical Research, University of Navarra, Pamplona, Spain
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      address:
         name:Department of Immunology and Immunotherapy, Center for Applied Medical Research, University of Navarra, Pamplona, Spain
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      name:Weizmann Institute of Science
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         name:Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel
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               name:Department of Gene Therapy and Regulation of Gene Expression, Center for Applied Medical Research, University of Navarra, Pamplona, Spain
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            name:Institute of Health Research of Navarra (IdiSNA)
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            address:
               name:Department of Gene Therapy and Regulation of Gene Expression, Center for Applied Medical Research, University of Navarra, Pamplona, Spain
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            address:
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            address:
               name:Institute of Health Research of Navarra (IdiSNA), Pamplona, Spain
               type:PostalAddress
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            address:
               name:Department of Immunology and Immunotherapy, Center for Applied Medical Research, University of Navarra, Pamplona, Spain
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            name:Center for Applied Medical Research, University of Navarra
            address:
               name:Department of Gene Therapy and Regulation of Gene Expression, Center for Applied Medical Research, University of Navarra, Pamplona, Spain
               type:PostalAddress
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            name:Institute of Health Research of Navarra (IdiSNA)
            address:
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            name:Center for Applied Medical Research, University of Navarra
            address:
               name:Department of Gene Therapy and Regulation of Gene Expression, Center for Applied Medical Research, University of Navarra, Pamplona, Spain
               type:PostalAddress
            type:Organization
            name:Institute of Health Research of Navarra (IdiSNA)
            address:
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               type:PostalAddress
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      name:Elena Grossi
      affiliation:
            name:Center for Applied Medical Research, University of Navarra
            address:
               name:Department of Gene Therapy and Regulation of Gene Expression, Center for Applied Medical Research, University of Navarra, Pamplona, Spain
               type:PostalAddress
            type:Organization
            name:Institute of Health Research of Navarra (IdiSNA)
            address:
               name:Institute of Health Research of Navarra (IdiSNA), Pamplona, Spain
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      name:Shuling Guo
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            address:
               name:Department of Antisense Drug Discovery and Clinical Development, Ionis Pharmaceuticals, Carlsbad, USA
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            address:
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               type:PostalAddress
            type:Organization
            name:Center for Applied Medical Research, University of Navarra
            address:
               name:Department of Immunology and Immunotherapy, Center for Applied Medical Research, University of Navarra, Pamplona, Spain
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      name:Igor Ulitsky
      affiliation:
            name:Weizmann Institute of Science
            address:
               name:Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel
               type:PostalAddress
            type:Organization
      name:Maite Huarte
      affiliation:
            name:Center for Applied Medical Research, University of Navarra
            address:
               name:Department of Gene Therapy and Regulation of Gene Expression, Center for Applied Medical Research, University of Navarra, Pamplona, Spain
               type:PostalAddress
            type:Organization
            name:Institute of Health Research of Navarra (IdiSNA)
            address:
               name:Institute of Health Research of Navarra (IdiSNA), Pamplona, Spain
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Department of Gene Therapy and Regulation of Gene Expression, Center for Applied Medical Research, University of Navarra, Pamplona, Spain
      name:Institute of Health Research of Navarra (IdiSNA), Pamplona, Spain
      name:Present Address: Laboratory for Molecular Cancer Biology, Department of Oncology, KU Leuven, Leuven, Belgium
      name:Department of Gene Therapy and Regulation of Gene Expression, Center for Applied Medical Research, University of Navarra, Pamplona, Spain
      name:Institute of Health Research of Navarra (IdiSNA), Pamplona, Spain
      name:Department of Gene Therapy and Regulation of Gene Expression, Center for Applied Medical Research, University of Navarra, Pamplona, Spain
      name:Institute of Health Research of Navarra (IdiSNA), Pamplona, Spain
      name:Department of Gene Therapy and Regulation of Gene Expression, Center for Applied Medical Research, University of Navarra, Pamplona, Spain
      name:Institute of Health Research of Navarra (IdiSNA), Pamplona, Spain
      name:Department of Gene Therapy and Regulation of Gene Expression, Center for Applied Medical Research, University of Navarra, Pamplona, Spain
      name:Institute of Health Research of Navarra (IdiSNA), Pamplona, Spain
      name:Institute of Health Research of Navarra (IdiSNA), Pamplona, Spain
      name:Department of Immunology and Immunotherapy, Center for Applied Medical Research, University of Navarra, Pamplona, Spain
      name:Department of Gene Therapy and Regulation of Gene Expression, Center for Applied Medical Research, University of Navarra, Pamplona, Spain
      name:Institute of Health Research of Navarra (IdiSNA), Pamplona, Spain
      name:Department of Gene Therapy and Regulation of Gene Expression, Center for Applied Medical Research, University of Navarra, Pamplona, Spain
      name:Institute of Health Research of Navarra (IdiSNA), Pamplona, Spain
      name:Department of Gene Therapy and Regulation of Gene Expression, Center for Applied Medical Research, University of Navarra, Pamplona, Spain
      name:Institute of Health Research of Navarra (IdiSNA), Pamplona, Spain
      name:Department of Antisense Drug Discovery and Clinical Development, Ionis Pharmaceuticals, Carlsbad, USA
      name:Institute of Health Research of Navarra (IdiSNA), Pamplona, Spain
      name:Department of Immunology and Immunotherapy, Center for Applied Medical Research, University of Navarra, Pamplona, Spain
      name:Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel
      name:Department of Gene Therapy and Regulation of Gene Expression, Center for Applied Medical Research, University of Navarra, Pamplona, Spain
      name:Institute of Health Research of Navarra (IdiSNA), Pamplona, Spain

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