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The lncRNA MIR31HG regulates p16(INK4A) expression to modulate senescence

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DOI

  • Marta Montes, University of Copenhagen
  • ,
  • Morten M. Nielsen
  • Giulia Maglieri, University of Copenhagen
  • ,
  • Anders Jacobsen, Mem Sloan Kettering Canc Ctr, Memorial Sloan Kettering Cancer Center, Computat Biol Ctr
  • ,
  • Jonas Hojfeldt, University of Copenhagen
  • ,
  • Shuchi Agrawal-Singh, University of Copenhagen
  • ,
  • Klaus Hansen, University of Copenhagen
  • ,
  • Kristian Helin, University of Copenhagen
  • ,
  • Harmen J. G. van de Werken, Erasmus MC, Erasmus University Rotterdam, Dept Cell Biol
  • ,
  • Jakob S. Pedersen
  • Anders H. Lund, University of Copenhagen

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).

Original languageEnglish
Article number6967
JournalNature Communications
Volume6
Number of pages15
ISSN2041-1723
DOIs
Publication statusPublished - Apr 2015

    Research areas

  • LONG NONCODING RNA, ONCOGENE-INDUCED SENESCENCE, CELLULAR SENESCENCE, CHROMATIN INTERACTIONS, EPIGENETIC REGULATION, SECRETORY PHENOTYPE, TUMOR-SUPPRESSOR, GENE-EXPRESSION, MESSENGER-RNA, BREAST-CANCER

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