High-throughput sequencing of two populations of extracellular vesicles provides an mRNA signature that can be detected in the circulation of breast cancer patients

RNA Biol. 2017 Mar 4;14(3):305-316. doi: 10.1080/15476286.2016.1259061. Epub 2016 Nov 18.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor*
  • Breast Neoplasms / blood
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism*
  • Cell Cycle / genetics
  • Cell Line, Tumor
  • Computational Biology / methods
  • Cytosol / metabolism
  • E2F4 Transcription Factor / metabolism
  • Extracellular Vesicles / metabolism*
  • Female
  • Gene Expression Profiling
  • Gene Ontology
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Protein Sorting Signals / genetics
  • RNA, Messenger / blood
  • RNA, Messenger / genetics*
  • Transcriptome
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism


  • Biomarkers, Tumor
  • E2F4 Transcription Factor
  • Protein Sorting Signals
  • RNA, Messenger
  • Vascular Endothelial Growth Factor A