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The lncRNA MIR31HG regulates p16(INK4A) expression to modulate senescence.
Montes, Marta; Nielsen, Morten M; Maglieri, Giulia; Jacobsen, Anders; Højfeldt, Jonas; Agrawal-Singh, Shuchi; Hansen, Klaus; Helin, Kristian; van de Werken, Harmen J G; Pedersen, Jakob S; Lund, Anders H.
Afiliação
  • Montes M; Biotech Research and Innovation Centre, University of Copenhagen, Ole Maaloes Vej 5, Copenhagen 2200, Denmark.
  • Nielsen MM; Department of Molecular Medicine, Århus University Hospital, Skejby, Århus N 8200, Denmark.
  • Maglieri G; Biotech Research and Innovation Centre, University of Copenhagen, Ole Maaloes Vej 5, Copenhagen 2200, Denmark.
  • Jacobsen A; Computational Biology Center, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA.
  • Højfeldt J; Biotech Research and Innovation Centre, University of Copenhagen, Ole Maaloes Vej 5, Copenhagen 2200, Denmark.
  • Agrawal-Singh S; Centre for Epigenetics, University of Copenhagen, Copenhagen 2200, Denmark.
  • Hansen K; Biotech Research and Innovation Centre, University of Copenhagen, Ole Maaloes Vej 5, Copenhagen 2200, Denmark.
  • Helin K; Centre for Epigenetics, University of Copenhagen, Copenhagen 2200, Denmark.
  • van de Werken HJG; Biotech Research and Innovation Centre, University of Copenhagen, Ole Maaloes Vej 5, Copenhagen 2200, Denmark.
  • Pedersen JS; Centre for Epigenetics, University of Copenhagen, Copenhagen 2200, Denmark.
  • Lund AH; Biotech Research and Innovation Centre, University of Copenhagen, Ole Maaloes Vej 5, Copenhagen 2200, Denmark.
Nat Commun ; 6: 6967, 2015 Apr 24.
Article em En | MEDLINE | ID: mdl-25908244
ABSTRACT
Oncogene-induced senescence (OIS) can occur in response to oncogenic insults and is considered an important tumour suppressor mechanism. Here we identify the lncRNA MIR31HG as upregulated in OIS and find that knockdown of MIR31HG promotes a strong p16(INK4A)-dependent senescence phenotype. Under normal conditions, MIR31HG is found in both nucleus and cytoplasm, but following B-RAF expression MIR31HG is located mainly in the cytoplasm. We show that MIR31HG interacts with both INK4A and MIR31HG genomic regions and with Polycomb group (PcG) proteins, and that MIR31HG is required for PcG-mediated repression of the INK4A locus. We further identify a functional enhancer, located between MIR31HG and INK4A, which becomes activated during OIS and interacts with the MIR31HG promoter. Data from melanoma patients show a negative correlation between MIR31HG and p16(INK4A) expression levels, suggesting a role for this transcript in cancer. Hence, our data provide a new lncRNA-mediated regulatory mechanism for the tumour suppressor p16(INK4A).
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Senescência Celular / Inibidor p16 de Quinase Dependente de Ciclina / Proteínas Proto-Oncogênicas B-raf / RNA Longo não Codificante / Melanoma Limite: Animals / Humans Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2015 Tipo de documento: Article País de afiliação: Dinamarca

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Senescência Celular / Inibidor p16 de Quinase Dependente de Ciclina / Proteínas Proto-Oncogênicas B-raf / RNA Longo não Codificante / Melanoma Limite: Animals / Humans Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2015 Tipo de documento: Article País de afiliação: Dinamarca