Title: | Epigenetic inactivation of the splicing RNA-binding protein CELF2 in human breast cancer |
Author: |
... 5 more authors Show all authors |
Date: | 2019-08-13 |
Language: | English |
Scope: | 7106-7112 |
University/Institute: | Háskóli Íslands University of Iceland |
School: | Heilbrigðisvísindasvið (HÍ) School of Health Sciences (UI) |
Department: | Læknadeild (HÍ) Faculty of Medicine (UI) Lífvísindasetur (HÍ) Biomedical Center (UI) |
Series: | Oncogene;38(45) |
ISSN: | 0950-9232 1476-5594 (eISSN) |
DOI: | 10.1038/s41388-019-0936-x |
Subject: | Cancer genomics; Prognostic markers; Genamengi; Erfðafræði; Brjóstakrabbamein |
URI: | https://hdl.handle.net/20.500.11815/1588 |
Citation:Piqué, L., Martinez de Paz, A., Piñeyro, D. et al. Epigenetic inactivation of the splicing RNA-binding protein CELF2 in human breast cancer. Oncogene 38, 7106–7112 (2019). https://doi.org/10.1038/s41388-019-0936-x
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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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Description:Publisher's version (útgefin grein).
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Rights:Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
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