The landscape of antisense gene expression in human cancers
- O. Alejandro Balbin1,2,3,
- Rohit Malik1,2,7,
- Saravana M. Dhanasekaran1,2,7,
- John R. Prensner1,2,
- Xuhong Cao1,2,
- Yi-Mi Wu1,2,
- Dan Robinson1,2,
- Rui Wang1,2,
- Guoan Chen4,
- David G. Beer4,
- Alexey I. Nesvizhskii1,2,3,8 and
- Arul M. Chinnaiyan1,2,3,5,6,8
- 1Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan 48109, USA;
- 2Department of Pathology, University of Michigan, Ann Arbor, Michigan 48109, USA;
- 3Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan 48109, USA;
- 4Department of Surgery, Section of Thoracic Surgery, University of Michigan, Ann Arbor, Michigan 48109, USA;
- 5Department of Urology, University of Michigan, Ann Arbor, Michigan 48109, USA;
- 6Comprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan 48109, USA
- Corresponding authors: arul{at}umich.edu, nesvi{at}med.umich.edu
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↵7 These authors contributed equally to this work.
Abstract
High-throughput RNA sequencing has revealed more pervasive transcription of the human genome than previously anticipated. However, the extent of natural antisense transcripts’ (NATs) expression, their regulation of cognate sense genes, and the role of NATs in cancer remain poorly understood. Here, we use strand-specific paired-end RNA sequencing (ssRNA-seq) data from 376 cancer samples covering nine tissue types to comprehensively characterize the landscape of antisense expression. We found consistent antisense expression in at least 38% of annotated transcripts, which in general is positively correlated with sense gene expression. Investigation of sense/antisense pair expressions across tissue types revealed lineage-specific, ubiquitous and cancer-specific antisense loci transcription. Comparisons between tumor and normal samples identified both concordant (same direction) and discordant (opposite direction) sense/antisense expression patterns. Finally, we provide OncoNAT, a catalog of cancer-related genes with significant antisense transcription, which will enable future investigations of sense/antisense regulation in cancer. Using OncoNAT we identified several functional NATs, including NKX2-1-AS1 that regulates the NKX2-1 oncogene and cell proliferation in lung cancer cells. Overall, this study provides a comprehensive account of NATs and supports a role for NATs' regulation of tumor suppressors and oncogenes in cancer biology.
Footnotes
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↵8 These authors share senior authorship.
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[Supplemental material is available for this article.]
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Article published online before print. Article, supplemental material, and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.180596.114.
- Received June 27, 2014.
- Accepted May 11, 2015.
This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
