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

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Authors
Piqué, Laia
Martinez de Paz, Alexia
Piñeyro, David
Martínez-Cardús, Anna
Castro de Moura, Manuel
Llinàs-Arias, Pere
Setien, Fernando
Gomez-Miragaya, Jorge
Gonzalez-Suarez, Eva
Sigurdsson, Stefan
Jonasson, Jon G
Villanueva, Alberto
Vidal, August
Davalos, Veronica
Esteller, Manel
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Issue Date
2019-11

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Piqué L, de Paz AM, Piñeyro D, Martínez-Cardús A, de Moura MC, Llinàs-Arias P, Setien F, Gomez-Miragaya J, Gonzalez-Suarez E, Sigurdsson S, Jonasson JG. Epigenetic inactivation of the splicing RNA-binding protein CELF2 in human breast cancer. Oncogene. 2019;38(45): 7106-7112.
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.
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https://www.nature.com/articles/s41388-019-0936-x
ae974a485f413a2113503eed53cd6c53
10.1038/s41388-019-0936-x
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English Journal Articles (Peer Reviewed)

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