High-throughput sequencing of two populations of extracellular vesicles provides an mRNA signature that can be detected in the circulation of breast cancer patients. Issue 3 (4th March 2017)

• Record Type: Journal Article
• Authors: Conley, Andrew; Minciacchi, Valentina R.; Lee, Dhong Hyun; Knudsen, Beatrice S.; Karlan, Beth Y.; Citrigno, Luigi; Viglietto, Giuseppe; Tewari, Muneesh; Freeman, Michael R.; Demichelis, Francesca; Di Vizio, Dolores
• Is Part Of: RNA biology. Volume 14:Issue 3(2017)
• Page Start: 305
• Page End: 316
• Publication Date: 2017-03-04
• Subjects: RNA -- Periodicals; Molecular biology -- Periodicals; Molecular biology; RNA; Periodicals; 572.8805
• DOI: 10.1080/15476286.2016.1259061
• Languages: English
• ISSNs: 1547-6286

Abstract

ABSTRACT: Extracellular vesicles (EVs) contain a wide range of RNA types with a reported prevalence of non-coding RNA. To date a comprehensive characterization of the protein coding transcripts in EVs is still lacking. We performed RNA-Sequencing (RNA-Seq) of 2 EV populations and identified a small fraction of transcripts that were expressed at significantly different levels in large oncosomes and exosomes, suggesting they may mediate specialized functions. However, these 2 EV populations exhibited a common mRNA signature that, in comparison to their donor cells, was significantly enriched in mRNAs encoding E2F transcriptional targets and histone proteins. These mRNAs are primarily expressed in the S-phase of the cell cycle, suggesting that they may be packaged into EVs during S-phase. In silico analysis using subcellular compartment transcriptome data from the ENCODE cell line compendium revealed that EV mRNAs originate from a cytoplasmic RNA pool. The EV signature was independently identified in plasma of patients with breast cancer by RNA-Seq. Furthermore, several transcripts differentially expressed in EVs from patients versus controls mirrored differential expression between normal and breast cancer tissues. Altogether, this largest high-throughput profiling of EV mRNA demonstrates that EVs carry tumor-specific alterations and can be interrogated as a source of cancer-derived cargo.