Abstract B02: Telomere-driven chromosome instability impacts on microRNA expression through epigenetic mechanisms

Abstract

Abstract Telomere shortening is a major source of chromosome instability (CIN) at early stages during carcinogenesis. However, the mechanisms through which telomere-driven CIN (T-CIN) contributes to the acquisition of tumor phenotypes remain uncharacterized. We have used human epithelial kidney cells (HEK cells), a well-established in vitro model of progressive telomere instability, to study the impact of T-CIN in the expression of miRs and the biological consequences that might be relevant for the acquisition of tumor phenotypes. We discovered that human epithelial kidney cells undergoing T-CIN display massive microRNA (miR) expression changes that are not related to local losses or gains. This widespread miR deregulation encompasses a miR-200-dependent epithelial-to-mesenchymal transition (EMT) that confers to immortalized pretumoral cells phenotypic traits of metastatic potential. Since deregulation of miRs in HEK CIN+ cells was widespread, orchestrated, and not related with copy number changes we hypothesized that this phenomenon utilizes epigenetic cues. Indeed, investigation of the mechanisms controlling miR-200 expression revealed that both DNA methylation and histone modifications changed significantly in cells undergoing T-CIN. Unbiased approaches are now being used to describe the epigenome changes genome-wide that are associated with CIN during cell transformation. Citation Format: Karina Jouravleva, Luis Castro-Vega, Arturo Londono-Vallejo. Telomere-driven chromosome instability impacts on microRNA expression through epigenetic mechanisms. [abstract]. In: Proceedings of the AACR Special Conference on Chromatin and Epigenetics in Cancer; Jun 19-22, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2013;73(13 Suppl):Abstract nr B02.