Article open access publication

The lncRNA MIR31HG regulates p16INK4A expression to modulate senescence

Nature Communications, Springer Nature, ISSN 2041-1723

Volume 6, 1, 2015

DOI:10.1038/ncomms7967, Dimensions: pub.1016873484, PMID: 25908244,

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  1. (1) University of Copenhagen, grid.5254.6, KU
  2. (2) Aarhus University Hospital, grid.154185.c, Central Denmark Region
  3. (3) Memorial Sloan Kettering Cancer Center, grid.51462.34
  4. (4) Erasmus University Medical Center, grid.5645.2
  5. (5) Aarhus University, grid.7048.b, AU

Description

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).

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University of Copenhagen

Aarhus University

Danish Open Access Indicator

2015: Realized

Research area: Science & Technology

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2015: Level 1

Research area: Science & Technology

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Times Cited: 104

Field Citation Ratio (FCR): 23.02

Relative Citation ratio (RCR): 4.09

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