A promoter-proximal transcript targeted by genetic polymorphism controls E-cadherin silencing in human cancers

• DOI: 10.1038/ncomms15622
• Publication Date: 2017-05-30T10:30:18Z
• Authors: Giuseppina Pisignano; Sara Napoli; Marco Magistri; Sarah N. Mapelli; Chiara Pastori; Stefano Di Marco; Gianluca Civenni; Domenico Albino; Claudia Enriquez; Sara Allegrini; Abhishek Mitra; Gioacchino D’Ambr...; Maurizia Mello-Grand; Giovanna Chiorino; Ramon Garcia-Escu...; Gabriele Varani; Giuseppina M. Car...; Carlo V. Catapano
• Keywords: Argonaute; Dicer

Long noncoding RNAs are emerging players in the epigenetic machinery with key roles development and diseases. Here we uncover a complex network comprising promoter-associated RNA (paRNA), microRNA regulators that controls transcription of tumour suppressor E-cadherin epithelial cancers. silencing relies on formation between paRNA microRNA-guided Argonaute 1 that, together, recruit SUV39H1 induce repressive chromatin modifications gene promoter. A single nucleotide polymorphism (rs16260) linked to increased cancer risk alters secondary structure paRNA, allele facilitating assembly silencing. Collectively, these data demonstrate role regulation impact genetic variant its function. Deregulation paRNA-based networks may contribute other diseases making them promising targets for drug discovery.