Targeting LINC00673 expression triggers cellular senescence in lung cancer. Issue 12 (2nd December 2018)

• Record Type: Journal Article
• Authors: Roth, Anna; Boulay, Karine; Groß, Matthias; Polycarpou-Schwarz, Maria; Mallette, Frédérick A.; Regnier, Marine; Bida, Or; Ginsberg, Doron; Warth, Arne; Schnabel, Philipp A.; Muley, Thomas; Meister, Michael; Zabeck, Heike; Hoffmann, Hans; Diederichs, Sven
• Is Part Of: RNA biology. Volume 15:Issue 12(2018)
• Page Start: 1499
• Page End: 1511
• Publication Date: 2018-12-02
• Subjects: LINC00673 -- long noncoding RNA -- lung cancer -- p53 -- senescence; RNA -- Periodicals; Molecular biology -- Periodicals; Molecular biology; RNA; Periodicals; 572.8805
• DOI: 10.1080/15476286.2018.1553481
• Languages: English
• ISSNs: 1547-6286

Abstract

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.