Epigenetic inactivation of the p53-induced long noncoding RNA TP53 target 1 in human cancer

Significance Long noncoding RNAs (lncRNAs) are starting to be recognized as critical molecules for cellular transformation, although only a few candidates have so far been characterized. Here we report that TP53TG1 is an lncRNA that is critical for the correct response of p53 to DNA damage. The cancer growth suppressor features of TP53TG1 are linked to its ability to block the tumorigenic activity of the RNA binding protein YBX1. The DNA methylation-associated silencing of TP53TG1 produces aggressive tumors that are resistant to cellular death when DNA-damaging agents and small targeted molecules are used. Our study provides an example of a tumor suppressor lncRNA undergoing an epigenetic lesion in cancer that is placed at the crossroads of DNA damage and oncogenic pathways.