English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/168521
logo share SHARE logo core CORE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL
Exportar a otros formatos:


Gene amplification-associated overexpression of the RNA editing enzyme ADAR1 enhances human lung tumorigenesis

AuthorsAnadón, C.; Guil, S.; Simó-Riudalbas, L.; Moutinho, C.; Setien, F.; Martínez-Cardús, A.; Moran, S.; Villanueva, A.; Calaf, M.; Vidal, August; Lazo, Pedro A. ; Zondervan, I.; Savola, S.; Kohno, T.; Yokota, J.; Pouplana, L. R. de; Esteller, M.
Issue Date2016
PublisherNature Publishing Group
CitationOncogene 35(33): 4407-4413 (2016)
AbstractThe introduction of new therapies against particular genetic mutations in non-small-cell lung cancer is a promising avenue for improving patient survival, but the target population is small. There is a need to discover new potential actionable genetic lesions, to which end, non-conventional cancer pathways, such as RNA editing, are worth exploring. Herein we show that the adenosine-toinosine editing enzyme ADAR1 undergoes gene amplification in non-small cancer cell lines and primary tumors in association with higher levels of the corresponding mRNA and protein. From a growth and invasion standpoint, the depletion of ADAR1 expression in amplified cells reduces their tumorigenic potential in cell culture and mouse models, whereas its overexpression has the opposite effects. From a functional perspective, ADAR1 overexpression enhances the editing frequencies of target transcripts such as NEIL1 and miR-381. In the clinical setting, patients with early-stage lung cancer, but harboring ADAR1 gene amplification, have poor outcomes. Overall, our results indicate a role for ADAR1 as a lung cancer oncogene undergoing gene amplification-associated activation that affects downstream RNA editing patterns and patient prognosis.
Publisher version (URL)https://doi.org/10.1038/onc.2015.469
Identifiersdoi: 10.1038/onc.2015.469
issn: 0950-9232
e-issn: 1476-5594
Appears in Collections:(IBMCC) Artículos
Files in This Item:
File Description SizeFormat 
genadar1.pdf2,42 MBUnknownView/Open
Show full item record
Review this work

Related articles:

WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.