The landscape of human p53-regulated long non-coding RNAs reveals critical host gene co-regulation.

The role of long non-protein-coding RNAs (lncRNAs) in p53-mediated tumor suppression has become increasingly appreciated in the past decade. Thus, the identification of p53-regulated lncRNAs can be a promising starting point to select and prioritize lncRNAs for functional analyses. By integrating transcriptome and transcription factor binding data, we identified 379 lncRNAs that are recurrently differentially regulated by p53. Dissecting the mechanisms by which p53 regulates many of them, we identified sets of lncRNAs regulated either directly by p53 or indirectly through the p53-RFX7 and p53-p21-DREAM/RB:E2F pathways. Importantly, we identified multiple p53-responsive lncRNAs that are co-regulated with their protein-coding host genes, revealing an important mechanism by which p53 may regulate lncRNAs. Further analysis of transcriptome data and clinical data from cancer patients showed that recurrently p53-regulated lncRNAs are associated with patient survival. Together, the integrative analysis of the landscape of p53-regulated lncRNAs provides a powerful resource facilitating the identification of lncRNA function and displays the mechanisms of p53-dependent regulation that could be exploited for developing anti-cancer approaches.