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http://hdl.handle.net/2445/156079
Title: | Epigenetic inactivation of the splicing RNA-binding protein CELF2 in human breast cancer |
Author: | Piqué, Laia Martínez de Paz, Alexia Piñeyro, David Martínez Cardús, Anna Castro de Moura, Manuel Llinàs-Arias, Pere Setién, Fernando Gómez Miragaya, Jorge González Suárez, Eva Sigurdsson, Stefan Jonasson, Jon G. Villanueva Garatachea, Alberto Vidal-Bel, August Davalos, Veronica Esteller, Manel |
Keywords: | Càncer de mama Proteïnes Teixit nerviós ADN Metilació RNA Breast cancer Proteins Nerve tissue DNA Methylation RNA |
Issue Date: | 1-Nov-2019 |
Publisher: | Macmillan Publishers |
Abstract: | Human tumors show altered patterns of protein isoforms that can be related to the dysregulation of messenger RNA alternative splicing also observed in transformed cells. Although somatic mutations in core spliceosome components and their associated factors have been described in some cases, almost nothing is known about the contribution of distorted epigenetic patterns to aberrant splicing. Herein, we show that the splicing RNA-binding protein CELF2 is targeted by promoter hypermethylation-associated transcriptional silencing in human cancer. Focusing on the context of breast cancer, we also demonstrate that CELF2 restoration has growth-inhibitory effects and that its epigenetic loss induces an aberrant downstream pattern of alternative splicing, affecting key genes in breast cancer biology such as the autophagy factor ULK1 and the apoptotic protein CARD10. Furthermore, the presence of CELF2 hypermethylation in the clinical setting is associated with shorter overall survival of the breast cancer patients carrying this epigenetic lesion. |
Note: | Reproducció del document publicat a: https://doi.org/10.1038/s41388-019-0936-x |
It is part of: | Oncogene, 2019, vol. 38, num. 45, p. 7106-7112 |
URI: | http://hdl.handle.net/2445/156079 |
Related resource: | https://doi.org/10.1038/s41388-019-0936-x |
ISSN: | 0950-9232 |
Appears in Collections: | Articles publicats en revistes (Patologia i Terapèutica Experimental) Articles publicats en revistes (Ciències Fisiològiques) Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
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