The lncRNA MIR31HG regulates p16 INK4A expression to modulate senescence Journal Article
| Authors: | Montes, M.; Nielsen, M. M.; Maglieri, G.; Jacobsen, A.; Højfeldt, J.; Agrawal-Singh, S.; Hansen, K.; Helin, K.; Van De Werken, H. J. G.; Pedersen, J. S.; Lund, A. H. |
| Article 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 p16INK4A -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 p16INK4A expression levels, suggesting a role for this transcript in cancer. Hence, our data provide a new lncRNA-mediated regulatory mechanism for the tumour suppressor p16INK4A. © 2015 Macmillan Publishers Limited. All rights reserved. |
| Keywords: | controlled study; unclassified drug; human cell; promoter region; phenotype; gene; melanoma; gene expression; protein protein interaction; gene locus; gene expression regulation; oncogene; regulatory mechanism; transcription regulation; gene repression; cytoplasm; genomics; upregulation; cell nucleus; senescence; cyclin dependent kinase inhibitor 2a; cell aging; b raf kinase; polycomb group protein; enhancer region; cancer; human; article; long untranslated rna; mir31hg protein |
| Journal Title: | Nature Communications |
| Volume: | 6 |
| ISSN: | 2041-1723 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2015-04-24 |
| Start Page: | 6967 |
| Language: | English |
| DOI: | 10.1038/ncomms7967 |
| PROVIDER: | scopus |
| PUBMED: | 25908244 |
| DOI/URL: | |
| Notes: | Export Date: 3 June 2015 -- Source: Scopus |
