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

Details

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State: Public
Version: Final published version
Serval ID
serval:BIB_1BADDEDD8870
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
A promoter-proximal transcript targeted by genetic polymorphism controls E-cadherin silencing in human cancers.
Journal
Nature communications
Author(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
Publication state
Published
Issued date
30/05/2017
Peer-reviewed
Oui
Volume
8
Pages
15622
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Abstract
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.
Keywords
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
Yes
Create date
06/06/2017 19:31
Last modification date
21/11/2022 9:21
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