Targeting LINC00673 expression triggers cellular senescence in lung cancer
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...
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| Main Authors: | , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
7 December 2018
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| In: |
RNA biology
Year: 2018, Volume: 15, Issue: 12, Pages: 1499-1511 |
| ISSN: | 1555-8584 |
| DOI: | 10.1080/15476286.2018.1553481 |
| Online Access: | Verlag, Volltext: https://doi.org/10.1080/15476286.2018.1553481
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| Author Notes: | 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 |
| Summary: | 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. |
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| Item Description: | Gesehen am 18.04.2019 |
| Physical Description: | Online Resource |
| ISSN: | 1555-8584 |
| DOI: | 10.1080/15476286.2018.1553481 |