Coding and noncoding landscape of extracellular RNA released by human glioma stem cells

Nat Commun. 2017 Oct 26;8(1):1145. doi: 10.1038/s41467-017-01196-x.

Abstract

Tumor-released RNA may mediate intercellular communication and serve as biomarkers. Here we develop a protocol enabling quantitative, minimally biased analysis of extracellular RNAs (exRNAs) associated with microvesicles, exosomes (collectively called EVs), and ribonucleoproteins (RNPs). The exRNA complexes isolated from patient-derived glioma stem-like cultures exhibit distinct compositions, with microvesicles most closely reflecting cellular transcriptome. exRNA is enriched in small ncRNAs, such as miRNAs in exosomes, and precisely processed tRNA and Y RNA fragments in EVs and exRNPs. EV-enclosed mRNAs are mostly fragmented, and UTRs enriched; nevertheless, some full-length mRNAs are present. Overall, there is less than one copy of non-rRNA per EV. Our results suggest that massive EV/exRNA uptake would be required to ensure functional impact of transferred RNA on brain recipient cells and predict the most impactful miRNAs in such conditions. This study also provides a catalog of diverse exRNAs useful for biomarker discovery and validates its feasibility on cerebrospinal fluid.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Brain Neoplasms / genetics
  • Brain Neoplasms / pathology
  • Cells, Cultured
  • Extracellular Vesicles / genetics*
  • Gene Expression Regulation, Neoplastic
  • Glioma / genetics
  • Glioma / pathology
  • Humans
  • Mice, Inbred C57BL
  • MicroRNAs / genetics
  • Neoplastic Stem Cells / metabolism*
  • RNA, Messenger / genetics*
  • RNA, Neoplasm / genetics*
  • RNA, Untranslated / genetics*
  • Transcriptome
  • Tumor Cells, Cultured

Substances

  • MicroRNAs
  • RNA, Messenger
  • RNA, Neoplasm
  • RNA, Untranslated