A promoter-proximal transcript targeted by genetic polymorphism controls E-cadherin silencing in human cancers.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 28555645.
- Also identified by DOI 10.1038/ncomms15622 and PMC identifier 5459991.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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.
Medical subject headings
- Argonaute Proteins
- Cadherins
- Eukaryotic Initiation Factors
- Gene Silencing
- Methyltransferases
- Neoplasms
- Prostatic Neoplasms
- Repressor Proteins