Targeting <i>LINC00673</i> 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 <i>LINC00673</i> with elevated expression in matched tumor versus normal tissue. We report that loss of <i>LINC00673</i> 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. <i>LINC00673</i>-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 <i>LINC00673</i> knockdown. In addition, we uncover that depletion of p53 in normal and tumor cells is sufficient to overcome <i>LINC00673</i>-mediated cell cycle arrest and cellular senescence. Furthermore, we report that overexpression of <i>LINC00673</i> reduces p53 translation and contributes to the bypass of Ras-induced senescence. In summary, our findings highlight <i>LINC00673</i> as a crucial regulator of proliferation and cellular senescence in lung cancer.