A promoter-proximal transcript targeted by genetic polymorphism controls E-cadherin silencing in human cancers.
Nat Commun
; 8: 15622, 2017 05 30.
Article
em En
| MEDLINE
| ID: mdl-28555645
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Próstata
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Proteínas Repressoras
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Caderinas
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Inativação Gênica
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Fatores de Iniciação em Eucariotos
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Proteínas Argonautas
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Metiltransferases
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Neoplasias
Limite:
Humans
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Male
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article