LINC02593 impedes cell senescence via COP1-mediated p53 degradation in cervical cancer

Evasion of cellular senescence is one of the hallmarks of cervical carcinoma (CC) to maintain malignant development. Even though the regulators driving CC cell senescence are widely recognized, the underlying upstream mechanisms are still not fully understood. Long non-coding RNAs (lncRNAs) are emerging as important regulators in cell senescence. Here, we conducted a lncRNA profiling and identified LINC02593 as a significantly downregulated lncRNA in induced senescent cervical squamous cell carcinoma (CSCC) cells. LINC02593 is upregulated in CSCC tissues. Depletion of LINC02593 resulted in a marked cellular senescence phenotype and tumor growth inhibition in vitro and in vivo, whereas LINC02593 overexpression suppressed doxorubicin-induced cell senescence. LINC02593 was shown to impede cell senescence by inhibiting p21 expression, and this regulation was mainly dependent on p53 protein degradation. Mechanistically, LINC02593 served as a scaffold, bridging the coiled-coil domain of COP1 and the C-terminal domain of p53, enhancing the affinity between p53 and its E3 ubiquitin ligase COP1. The "scaffold" function facilitated p53 degradation by COP1 as well as the downstream p21 repression, eventually evading cell senescence. Overall, we characterized a previously unknown mechanism by which LINC02593 manipulated senescence to promote CC progression.