Abstract:
:The 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-to-inosine 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.
journal_name
Oncogenejournal_title
Oncogeneauthors
Anadón C,Guil S,Simó-Riudalbas L,Moutinho C,Setien F,Martínez-Cardús A,Moran S,Villanueva A,Calaf M,Vidal A,Lazo PA,Zondervan I,Savola S,Kohno T,Yokota J,Ribas de Pouplana L,Esteller Mdoi
10.1038/onc.2015.469subject
Has Abstractpub_date
2016-08-18 00:00:00pages
4407-13issue
33eissn
0950-9232issn
1476-5594pii
onc2015469journal_volume
35pub_type
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