Transcriptome and long noncoding RNA sequencing of three extracellular vesicle subtypes released from the human colon cancer LIM1863 cell line

Sci Rep. 2016 Dec 5;6:38397. doi: 10.1038/srep38397.


Previously we reported that LIM1863 colorectal cancer (CRC) cells secrete three distinct extracellular vesicle subtypes - two subpopulations of exosomes (apical EpCAM-Exos and basolateral A33-Exos) and shed microvesicles (sMVs) - with distinct protein and miRNA signatures. Here, we extend our omics approach to understand the fundamental role of LIM1863-derived EVs by performing a comprehensive analysis of their mRNAs and long non-coding RNAs (lncRNAs) using RNA-Seq. We show that 2,389 mRNAs, 317 pseudogene transcripts, 1,028 lncRNAs and 206 short non-coding RNAs selectively distributed to (i.e., are enriched in) LIM1863 EVs, relative to the parent cell. An Ensembl/UniProtKB analysis revealed 1,937 mRNAs encode canonical proteins, 348 isoforms (including splice-variant proteins), and 119 'missing proteins' (i.e., annotated in Ensembl but not UniProtKB). Further dissection of our protein/RNA data revealed that 6/151 observed RNA binding proteins have the potential to interact with ~75% of EV-enriched RNAs. Intriguingly, the co-existence of U1 and U2 ribonucleoproteins and their cognate snRNAs in LIM1863 EVs suggests a possible association of CRC EVs with recipient cell splicing events. Our data reveal several potential lncRNA CRC biomarkers and novel splicing/fusion genes that, collectively, will advance our understanding of EV biology in CRC and accelerate the development of EV-based diagnostics and therapeutics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / metabolism
  • Cell Line, Tumor
  • Cell-Derived Microparticles / chemistry
  • Cell-Derived Microparticles / metabolism
  • Colonic Neoplasms / diagnosis*
  • Colonic Neoplasms / genetics*
  • Colonic Neoplasms / pathology
  • Databases, Factual
  • Exosomes / chemistry
  • Exosomes / metabolism
  • Gene Expression Regulation, Neoplastic*
  • Gene Ontology
  • Humans
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Molecular Sequence Annotation
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism
  • RNA, Neoplasm / genetics*
  • RNA, Neoplasm / metabolism
  • Ribonucleoprotein, U1 Small Nuclear / genetics
  • Ribonucleoprotein, U1 Small Nuclear / metabolism
  • Ribonucleoprotein, U2 Small Nuclear / genetics
  • Ribonucleoprotein, U2 Small Nuclear / metabolism
  • Transcriptome*


  • Biomarkers, Tumor
  • MicroRNAs
  • RNA, Long Noncoding
  • RNA, Neoplasm
  • Ribonucleoprotein, U1 Small Nuclear
  • Ribonucleoprotein, U2 Small Nuclear