A non-coding RNA network influenced by genetic polymorphism controls E-cadherin expression in human cancers

Diplôme Thèse A non-coding RNA network influenced by genetic polymorphism controls E-cadherin expression in human cancers eng 2016-12-07 author Pisignano Giuseppina 764754 director Scapozza Leonardo 600318 director Catapano Carlo 10.13097/archive-ouverte/unige:93953 urn:nbn:ch:unige-939533 Sc. 5037 Reduced expression of E-cadherin, encoded by the CDH1 gene, is frequent in epithelial tumours and is associated with the acquisition of invasive, stem cell-like and metastatic properties. However, the molecular mechanisms underlying the loss of E-cadherin expression are not fully understood. In this project, we uncover a complex network comprising a promoter- associated noncoding RNA (paRNA), microRNA and epigenetic regulators that controls transcription of 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. Notably, we found that 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. Dewey 615 31 Section des sciences pharmaceutiques 17 false d26a5b29-dfc8-4e56-9304-5d3a09c1305c Thesis Public Pisignano Giuseppina - Thesis 14.02.17.pdf 9073802 application/pdf openAccess Faculté des sciences / Section des sciences pharmaceutiques

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A non-coding RNA network influenced by genetic polymorphism controls E-cadherin expression in human cancers				2016	840	612

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