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EBioMedicine. 2018 Jan;27:167-175. doi: 10.1016/j.ebiom.2017.12.005. Epub 2017 Dec 6.

Global Transcriptome Analysis of RNA Abundance Regulation by ADAR in Lung Adenocarcinoma.

Author information

1
Department of Biomedical Informatics, The Ohio State University, Columbus, OH, United States.
2
Institute for Computational Health Sciences, University of California San Francisco, San Francisco, CA, United States.
3
Vet Path Services, Inc., Cincinnati, OH, United States.
4
Comprehensive Cancer Center, The Ohio State University, Columbus, OH, United States.
5
Canary Center for Cancer Early Detection, Stanford University, Palo Alto, CA, United States. Electronic address: paragm@stanford.edu.
6
Department of Biomedical Informatics, The Ohio State University, Columbus, OH, United States; Current Address: Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, United States. Electronic address: kunhuang@iu.edu.

Abstract

Despite tremendous advances in targeted therapies against lung adenocarcinoma, the majority of patients do not benefit from personalized treatments. A deeper understanding of potential therapeutic targets is crucial to increase the survival of patients. One promising target, ADAR, is amplified in 13% of lung adenocarcinomas and in-vitro studies have demonstrated the potential of its therapeutic inhibition to inhibit tumor growth. ADAR edits millions of adenosines to inosines within the transcriptome, and while previous studies of ADAR in cancer have solely focused on protein-coding edits, >99% of edits occur in non-protein coding regions. Here, we develop a pipeline to discover the regulatory potential of RNA editing sites across the entire transcriptome and apply it to lung adenocarcinoma tumors from The Cancer Genome Atlas. This method predicts that 1413 genes contain regulatory edits, predominantly in non-coding regions. Genes with the largest numbers of regulatory edits are enriched in both apoptotic and innate immune pathways, providing a link between these known functions of ADAR and its role in cancer. We further show that despite a positive association between ADAR RNA expression and apoptotic and immune pathways, ADAR copy number is negatively associated with apoptosis and several immune cell types' signatures.

KEYWORDS:

ADAR; Bioinformatics; Cancer; Lung adenocarcinoma; Post-transcriptional regulation; RNA editing

PMID:
29273356
PMCID:
PMC5828651
DOI:
10.1016/j.ebiom.2017.12.005
[Indexed for MEDLINE]
Free PMC Article

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