Author:
Balbin O. Alejandro,Malik Rohit,Dhanasekaran Saravana M.,Prensner John R.,Cao Xuhong,Wu Yi-Mi,Robinson Dan,Wang Rui,Chen Guoan,Beer David G.,Nesvizhskii Alexey I.,Chinnaiyan Arul M.
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.
Funder
US National Institutes of Health Prostate Specialized Program of Research Excellence
Early Detection Research Network
Prostate Cancer Foundation
Howard Hughes Medical Institute
American Cancer Society
Taubman Scholar of the University of Michigan
US National Institutes of Health
F31 National Institutes of Health Ruth L. Kirschstein National Research Service Award
Promote Diversity in Health-Related Research
University of Michigan
US Department of Defense Post-doctoral award
Prostate Cancer Foundation Young Investigator Award
Prostate Cancer Foundation Young Investigator award
Publisher
Cold Spring Harbor Laboratory
Subject
Genetics (clinical),Genetics
Cited by
139 articles.
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