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2019-11-01

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cc-by (c) Piqué et al., 2019
Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/156079

Epigenetic inactivation of the splicing RNA-binding protein CELF2 in human breast cancer

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https://doi.org/10.1038/s41388-019-0936-x

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.

Subject

Càncer de mama, Proteïnes, Teixit nerviós, ADN, Metilació, RNA

Subject (English)

Breast cancer, Proteins, Nerve tissue, DNA, Methylation, RNA

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Articles publicats en revistes (Ciències Fisiològiques)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
Articles publicats en revistes (Patologia i Terapèutica Experimental)

Citation

PIQUÉ, Laia, et al. Epigenetic inactivation of the splicing RNA-binding protein CELF2 in human breast cancer. Oncogene. 2019. Vol. 38, num. 45, pags. 7106-7112. ISSN 0950-9232. [consulted: 15 of August of 2026]. Available at: https://hdl.handle.net/2445/156079

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