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

被引：0
作者：
Laia Piqué
Alexia Martinez de Paz
David Piñeyro
Anna Martínez-Cardús
Manuel Castro de Moura
Pere Llinàs-Arias
Fernando Setien
Jorge Gomez-Miragaya
Eva Gonzalez-Suarez
Stefan Sigurdsson
Jon G. Jonasson
Alberto Villanueva
August Vidal
Veronica Davalos
Manel Esteller
机构：
[1] L’Hospitalet,Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL)
[2] Biomedical Center,Department of Biochemistry and Molecular Biology
[3] University of Iceland,Faculty of Medicine
[4] Landspitali University Hospital,Department of Pathology
[5] IDIBELL-Institut Catala d’Oncologia,Translational Research Laboratory
[6] Bellvitge University Hospital,Department of Pathology
[7] Centro de Investigacion Biomedica en Red Cancer (CIBERONC),Physiological Sciences Department, School of Medicine and Health Sciences
[8] Institucio Catalana de Recerca i Estudis Avançats (ICREA),undefined
[9] University of Barcelona (UB),undefined
[10] Josep Carreras Leukaemia Research Institute (IJC),undefined
[11] Badalona,undefined
来源：
Oncogene | 2019年 / 38卷
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摘要：
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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页码：7106 / 7112
页数：6
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