Given the vital role p53 plays in cancer, efforts have focused on finding a means of restoring functional p53 in human cancer cells. Normally lncRNAs exert a diverse spectrum of regulatory mechanisms, a special lncRNA NEAT1 (nuclear-enriched autosomal transcript) is mainly localized to nuclear paraspeckles, subnuclear particles that can be found in the cell nuclei of cancer cells . A recent study has illustrated that targeting NEAT1 and ‘paraspeckles’ would be a new therapeutic avenue in the fight against cancer (Figure 2A) . The authors have observed that NEAT1 is increased in Nutlin-3a-treated p53 wild type cancer cell lines. Strikingly, although NEAT1 is regulated by p53, it is required for the survival of highly dividing cancer initiating cells and that mice lacking NEAT1 are protected from developing skin cancer . NEAT1 depleted cancer cells exhibited a much higher level of γH2A.X accumulation and this higher amount of DNA damage was exacerbated in response to replication stress . These surprising results suggest that cancer cells can ‘hijack’ the survival principle of NEAT1 for their own good. However, there is still a long way to go before the information can be harnessed to help cure cancer. For instance, how exactly NEAT1 confers its survival functions to cells is worth further investigation. Interestingly, the most recent study has found that some NEAT1 isoforms reside in numerous non-paraspeckle foci and exert distinct functions . Therefore, precise disruption of NEAT1 isoforms via genome editing tools is demanded in clinical trials for targeting overlapping transcripts.