Targeting LINC00673 expression triggers cellular senescence in lung cancer.
RNA Biol
; 15(12): 1499-1511, 2018.
Article
em En
| MEDLINE
| ID: mdl-30499379
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.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Regulação Neoplásica da Expressão Gênica
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Senescência Celular
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RNA Longo não Codificante
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Neoplasias Pulmonares
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article