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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
Teixit nerviós
Breast cancer
Nerve tissue
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:
It is part of: Oncogene, 2019, vol. 38, num. 45, p. 7106-7112
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ISSN: 0950-9232
Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
Articles publicats en revistes (Patologia i Terapèutica Experimental)
Articles publicats en revistes (Ciències Fisiològiques)

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