title: The landscape of antisense gene expression in human cancers.
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.
authors.affiliation: Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan 48109, USA; Department of Pathology, University of Michigan, Ann Arbor, Michigan 48109, USA; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan 48109, USA;
authors.forename: O Alejandro
authors.initials: OA
authors.lastname: Balbin
authors.affiliation: Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan 48109, USA; Department of Pathology, University of Michigan, Ann Arbor, Michigan 48109, USA;
authors.forename: Rohit
authors.initials: R
authors.lastname: Malik
authors.affiliation: Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan 48109, USA; Department of Pathology, University of Michigan, Ann Arbor, Michigan 48109, USA;
authors.forename: Saravana M
authors.initials: SM
authors.lastname: Dhanasekaran
authors.affiliation: Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan 48109, USA; Department of Pathology, University of Michigan, Ann Arbor, Michigan 48109, USA;
authors.forename: John R
authors.initials: JR
authors.lastname: Prensner
authors.affiliation: Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan 48109, USA; Department of Pathology, University of Michigan, Ann Arbor, Michigan 48109, USA;
authors.forename: Xuhong
authors.initials: X
authors.lastname: Cao
authors.affiliation: Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan 48109, USA; Department of Pathology, University of Michigan, Ann Arbor, Michigan 48109, USA;
authors.forename: Yi-Mi
authors.initials: YM
authors.lastname: Wu
authors.affiliation: Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan 48109, USA; Department of Pathology, University of Michigan, Ann Arbor, Michigan 48109, USA;
authors.forename: Dan
authors.initials: D
authors.lastname: Robinson
authors.affiliation: Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan 48109, USA; Department of Pathology, University of Michigan, Ann Arbor, Michigan 48109, USA;
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of Surgery, Section of Thoracic Surgery, University of Michigan, Ann Arbor, Michigan 48109, USA;
authors.forename: Guoan
authors.initials: G
authors.lastname: Chen
authors.affiliation: Department of Surgery, Section of Thoracic Surgery, University of Michigan, Ann Arbor, Michigan 48109, USA;
authors.forename: David G
authors.initials: DG
authors.lastname: Beer
authors.affiliation: Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan 48109, USA; Department of Pathology, University of Michigan, Ann Arbor, Michigan 48109, USA; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan 48109, USA;
authors.forename: Alexey I
authors.initials: AI
authors.lastname: Nesvizhskii
authors.affiliation: Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan 48109, USA; Department of Pathology, University of Michigan, Ann Arbor, Michigan 48109, USA; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan 48109, USA; Department of Urology, University of Michigan, Ann Arbor, Michigan 48109, USA; Comprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors.forename: Arul M
authors.initials: AM
authors.lastname: Chinnaiyan
mesh_terms: D016000:Cluster Analysis; D019295:Computational Biology / Q000379:methods; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D056426:Genetic Loci; D006801:Humans; D009369:Neoplasms / Q000235:genetics*; D009928:Organ Specificity / Q000235:genetics; D016372:RNA, Antisense / Q000235:genetics*; D059467:Transcriptome
chemical_list: D016372:RNA, Antisense