Epigenetic inactivation of the splicing RNA-binding protein CELF2 in human breast cancer
| Autor: | Piqué, L., Martinez de Paz, A., Piñeyro, D., Martínez Cardús, Anna, Castro de Moura, Manuel, Llinàs-Arias, P., Setien, F., Gomez-Miragaya, J., Gonzalez-Suarez, E., Sigurdsson, S., Jonasson, J. G., Villanueva, A., Vidal, A., Davalos, Veronica, Esteller, M., Universitat Autònoma de Barcelona |
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| Přispěvatelé: | Læknadeild (HÍ), Faculty of Medicine (UI), Lífvísindasetur (HÍ), Biomedical Center (UI), Heilbrigðisvísindasvið (HÍ), School of Health Sciences (UI), Háskóli Íslands, University of Iceland |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Cancer Research Spliceosome RNA Splicing ADN RNA-binding protein Breast Neoplasms Nerve Tissue Proteins Biology Methylation Epigenesis Genetic Càncer de mama 03 medical and health sciences Prognostic markers 0302 clinical medicine Breast cancer Brjóstakrabbamein Genamengi Genetics medicine Tumor Cells Cultured Cancer genomics CELF Proteins Humans Erfðafræði Epigenetics Molecular Biology Nerve tissue Messenger RNA Teixit nerviós Alternative splicing Cancer Proteins DNA DNA Methylation medicine.disease Gene Expression Regulation Neoplastic 030104 developmental biology 030220 oncology & carcinogenesis RNA splicing DNA methylation Cancer research Spliceosomes RNA Female Metilació Proteïnes |
| Zdroj: | Dipòsit Digital de la UB Universidad de Barcelona Dipòsit Digital de Documents de la UAB Universitat Autònoma de Barcelona |
| Popis: | Publisher's version (útgefin grein). 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. We thank CERCA Program/Generalitat de Catalunya for institutional support. This work was supported by the Health Department PERIS-project no. SLT/002/16/00374 and AGAURprojects nos. 2017SGR1080, 2014SGR633, and 2009SGR1315 of the Catalan Government (Generalitat de Catalunya); the Spanish Institute of Health Carlos III (ISCIII) project no. DTS16/00153 and Ministerio de Economía y Competitividad (MINECO) project no. SAF2014–55000-R, co-financed by the European Development Regional Fund, “A way to achieve Europe” ERDF; the Cellex Foundation; and “la Caixa” Banking Foundation (LCF/PR/PR15/ 11100003). |
| Databáze: | OpenAIRE |
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