Abstract
Once thought to be a part of the ‘dark matter’ of the genome, long non-coding RNAs (lncRNAs) are emerging as an integral functional component of the mammalian transcriptome. LncRNAs are a novel class of mRNA-like transcripts which, despite no known protein-coding potential, demonstrate a wide range of structural and functional roles in cellular biology. However, the magnitude of the contribution of lncRNA expression to normal human tissues and cancers has not been investigated in a comprehensive manner. In this study, we compiled 272 human serial analysis of gene expression (SAGE) libraries to delineate lncRNA transcription patterns across a broad spectrum of normal human tissues and cancers. Using a novel lncRNA discovery pipeline we parsed over 24 million SAGE tags and report lncRNA expression profiles across a panel of 26 different normal human tissues and 19 human cancers. Our findings show extensive, tissue-specific lncRNA expression in normal tissues and highly aberrant lncRNA expression in human cancers. Here, we present a first generation atlas for lncRNA profiling in cancer.
Highlights
Genome instability and mutation are a hallmark of cancer [1]
To explore long non-coding RNAs (lncRNAs) expression in the broadest range of human tissue types and cancer types, we downloaded 360 Gene Expression Omnibus (GEO) accessioned human short serial analysis of gene expression (SAGE) libraries comprised of libraries curated by the Cancer Genome Anatomy Project (324 libraries) and lung tissue and cancer datasets (36 libraries) (Table S1)
Long non-coding RNA discovery pipeline To generate lncRNA expression profiles, we developed a lncRNA discovery pipeline to map tag-to-lncRNA matches (Figure 2)
Summary
Genome instability and mutation are a hallmark of cancer [1]. Genetic and epigenetic changes result in aberrant expression of protein-coding genes and many classes of non-coding RNAs (ncRNAs), including microRNAs (miRNAs). Once thought to be the ‘dark matter’ of the genome, ncRNAs have emerged as an integral component of the mammalian transcriptome [3,4,5]. These enigmatic molecules are defined by lack of protein-coding sequence, yet can play both structural and functional roles in the cell [6,7]. NcRNAs can been grouped into two major classes, the small ncRNAs, which include miRNAs and other non-coding transcripts of less than 200 nucleotides (nt), and the more recently described lncRNAs, which range from 200 nt to .100 kilobases (kb) [8]
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