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

Détails

Ressource 1Télécharger: ncomms15622.pdf (1962.75 [Ko])
Etat: Public
Version: Final published version
ID Serval
serval:BIB_1BADDEDD8870
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
A promoter-proximal transcript targeted by genetic polymorphism controls E-cadherin silencing in human cancers.
Périodique
Nature communications
Auteur⸱e⸱s
Pisignano G., Napoli S., Magistri M., Mapelli S.N., Pastori C., Di Marco S., Civenni G., Albino D., Enriquez C., Allegrini S., Mitra A., D'Ambrosio G., Mello-Grand M., Chiorino G., Garcia-Escudero R., Varani G., Carbone G.M., Catapano C.V.
ISSN
2041-1723 (Electronic)
ISSN-L
2041-1723
Statut éditorial
Publié
Date de publication
30/05/2017
Peer-reviewed
Oui
Volume
8
Pages
15622
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Résumé
Long noncoding RNAs are emerging players in the epigenetic machinery with key roles in development and diseases. Here we uncover a complex network comprising a promoter-associated noncoding RNA (paRNA), microRNA and epigenetic regulators that controls transcription of the tumour suppressor E-cadherin in epithelial cancers. E-cadherin silencing relies on the formation of a complex between the paRNA and microRNA-guided Argonaute 1 that, together, recruit SUV39H1 and induce repressive chromatin modifications in the gene promoter. A single nucleotide polymorphism (rs16260) linked to increased cancer risk alters the secondary structure of the paRNA, with the risk allele facilitating the assembly of the microRNA-guided Argonaute 1 complex and gene silencing. Collectively, these data demonstrate the role of a paRNA in E-cadherin regulation and the impact of a noncoding genetic variant on its function. Deregulation of paRNA-based epigenetic networks may contribute to cancer and other diseases making them promising targets for drug discovery.
Mots-clé
Alleles, Antigens, CD, Argonaute Proteins/genetics, Cadherins/genetics, Cell Differentiation, Epigenesis, Genetic, Eukaryotic Initiation Factors/genetics, Gene Expression Regulation, Neoplastic, Gene Silencing, Genes, Tumor Suppressor, Humans, Male, Methyltransferases/genetics, Mutagenesis, Site-Directed, Neoplasms/genetics, Nucleic Acid Conformation, Polymorphism, Genetic, Polymorphism, Single Nucleotide, Promoter Regions, Genetic, Prostatic Neoplasms/genetics, Prostatic Neoplasms/metabolism, Repressor Proteins/genetics
Pubmed
Web of science
Open Access
Oui
Création de la notice
06/06/2017 18:31
Dernière modification de la notice
21/11/2022 8:21
Données d'usage