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Title: Neuronal Differentiation-Related Epigenetic Regulator ZRF1 Has Independent Prognostic Value in Neuroblastoma but Is Functionally Dispensable In Vitro
Author: Jiménez, Carlos
Antonelli, Roberta
Masanas, Marc
Soriano, Aroa
Devis Jauregui, Laura
Camacho, Jessica
Magdaleno, Ainara
Guillén, Gabriela
Hladun, Raquel
Jubierre, Luz
Roma, Josep
Llobet Navas, David
Sánchez De Toledo, Josep
Moreno, Lucas
Gallego, Soledad
Segura, Miguel F.
Keywords: Epigenètica
Issue Date: 28-Sep-2021
Publisher: MDPI AG
Abstract: Neuroblastoma is a pediatric tumor of the peripheral nervous system that accounts for up to ~15% of all cancer-related deaths in children. Recently, it has become evident that epigenetic deregulation is a relevant event in pediatric tumors such as high-risk neuroblastomas, and a determinant for processes, such as cell differentiation blockade and sustained proliferation, which promote tumor progression and resistance to current therapies. Thus, a better understanding of epigenetic factors implicated in the aggressive behavior of neuroblastoma cells is crucial for the development of better treatments. In this study, we characterized the role of ZRF1, an epigenetic activator recruited to genes involved in the maintenance of the identity of neural progenitors. We combined analysis of patient sample expression datasets with loss- and gain-of-function studies on neuroblastoma cell lines. Functional analyses revealed that ZRF1 is functionally dispensable for those cellular functions related to cell differentiation, proliferation, migration, and invasion, and does not affect the cellular response to chemotherapeutic agents. However, we found that high levels of ZRF1 mRNA expression are associated to shorter overall survival of neuroblastoma patients, even when those patients with the most common molecular alterations used as prognostic factors are removed from the analyses, thereby suggesting that ZRF1 expression could be used as an independent prognostic factor in neuroblastoma.
Note: Reproducció del document publicat a:
It is part of: Cancers, 2021, vol. 13, num. 19, p. 4845
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ISSN: 2072-6694
Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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