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

Oncogene. 2016 Aug 18;35(33):4407-13. doi: 10.1038/onc.2015.469. Epub 2015 Dec 7.


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.

MeSH terms

  • Adenosine Deaminase / genetics*
  • Cell Line, Tumor
  • Gene Amplification*
  • Humans
  • Lung Neoplasms / etiology*
  • Lung Neoplasms / genetics
  • Oncogenes
  • Proto-Oncogene Proteins p21(ras) / genetics
  • RNA Editing*
  • RNA-Binding Proteins / genetics*


  • KRAS protein, human
  • RNA-Binding Proteins
  • ADAR protein, human
  • Adenosine Deaminase
  • Proto-Oncogene Proteins p21(ras)