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

Marta Montes Resano; Morten M Nielsen; Giulia Maglieri; Anders Jacobsen; Jonas Højfeldt; Shuchi Agrawal-Singh; Klaus Hansen; Kristian Helin; Harmen J G van de Werken; Jakob S Pedersen; Anders H. Lund

doi:10.1038/ncomms7967

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

Marta Montes Resano, Morten M Nielsen, Giulia Maglieri, Anders Jacobsen, Jonas Højfeldt, Shuchi Agrawal-Singh, Klaus Hansen, Kristian Helin, Harmen J G van de Werken, Jakob S Pedersen, Anders H. Lund

108 Citations (Scopus)

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).

Original language	English
Journal	Nature Communications
Volume	6
Pages (from-to)	6967
ISSN	2041-1723
DOIs	https://doi.org/10.1038/ncomms7967
Publication status	Published - 24 Apr 2015

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@article{0de091f63f954c02ad6c9b40aa98919b,

title = "The lncRNA MIR31HG regulates p16(INK4A) expression to modulate senescence",

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).",

author = "{Montes Resano}, Marta and Nielsen, {Morten M} and Giulia Maglieri and Anders Jacobsen and Jonas H{\o}jfeldt and Shuchi Agrawal-Singh and Klaus Hansen and Kristian Helin and {van de Werken}, {Harmen J G} and Pedersen, {Jakob S} and Lund, {Anders H.}",

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doi = "10.1038/ncomms7967",

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T1 - The lncRNA MIR31HG regulates p16(INK4A) expression to modulate senescence

AU - Montes Resano, Marta

AU - Nielsen, Morten M

AU - Maglieri, Giulia

AU - Jacobsen, Anders

AU - Højfeldt, Jonas

AU - Agrawal-Singh, Shuchi

AU - Hansen, Klaus

AU - Helin, Kristian

AU - van de Werken, Harmen J G

AU - Pedersen, Jakob S

AU - Lund, Anders H.

PY - 2015/4/24

Y1 - 2015/4/24

N2 - 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).

AB - 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).

U2 - 10.1038/ncomms7967

DO - 10.1038/ncomms7967

M3 - Journal article

C2 - 25908244

SN - 2041-1723

VL - 6

SP - 6967

JO - Nature Communications

JF - Nature Communications

ER -

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

Abstract

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