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