Targeting LINC00673 expression triggers cellular senescence in lung cancer

Anna Roth, Karine Boulay, Matthias Groß, Maria Polycarpou-Schwarz, Frédérick A. Mallette, Marine Regnier, Or Bida, Doron Ginsberg, Arne Warth, Philipp A. Schnabel, Thomas Muley, Michael Meister, Heike Zabeck, Hans Hoffmann, Sven Diederichs

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

Aberrant expression of noncoding RNAs plays a critical role during tumorigenesis. To uncover novel functions of long non-coding RNA (lncRNA) in lung adenocarcinoma, we used a microarray-based screen identifying LINC00673 with elevated expression in matched tumor versus normal tissue. We report that loss of LINC00673 is sufficient to trigger cellular senescence, a tumor suppressive mechanism associated with permanent cell cycle arrest, both in lung cancer and normal cells in a p53-dependent manner. LINC00673-depleted cells fail to efficiently transit from G1- to S-phase. Using a quantitative proteomics approach, we confirm the modulation of senescence-associated genes as a result of LINC00673 knockdown. In addition, we uncover that depletion of p53 in normal and tumor cells is sufficient to overcome LINC00673-mediated cell cycle arrest and cellular senescence. Furthermore, we report that overexpression of LINC00673 reduces p53 translation and contributes to the bypass of Ras-induced senescence. In summary, our findings highlight LINC00673 as a crucial regulator of proliferation and cellular senescence in lung cancer.

Original languageEnglish
Pages (from-to)1499-1511
Number of pages13
JournalRNA Biology
Volume15
Issue number12
DOIs
StatePublished - 2 Dec 2018

Bibliographical note

Publisher Copyright:
© 2018, © 2018 Informa UK Limited, trading as Taylor & Francis Group.

Keywords

  • LINC00673
  • long noncoding RNA
  • lung cancer
  • p53
  • senescence

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