Functional Characterization of p53: Induced Noncoding Transcript (Lincpint)

Résumé

The p53 transcription factor regulates a complex transcriptional network that is crucial to maintain cellular homeostasis. Only recently it has become clear that p53 regulates the expression of several long intergenic noncoding RNAs (lincRNAs). One of them, named Lincpint (p53 induced noncoding transcript), is the subject of this study. Lincpint is a direct transcriptional target of p53. In mouse cells, Lincpint promotes cell proliferation and survival by regulating the expression of genes of the TGF-ß, MAPK and p53 pathways. Lincpint is a nuclear lincRNA that directly interacts with the Polycomb repressive complex 2 (PRC2), and is required for PRC2 targeting of specific genes for H3K27 tri-methylation and repression. Murine Lincpint has an ortholog in human (LINC-PINT), which presents suggestive analogies with the murine lincRNA, such as its regulation by p53. Its expression significantly correlates with the same cellular pathways as the mouse ortholog, including the p53 pathway. Interestingly, LINC-PINT is downregulated multiple tumor types. Its overexpression inhibits the proliferation, in vivo tumor growth and migration-invasion capability of tumor cells. Altogether, these data suggest a possible role of LINC-PINT as tumor suppressor.