Circular RNA expression profiles in extracellular vesicles from the plasma of patients with pancreatic ductal adenocarcinoma

FEBS Open Bio. 2019 Dec;9(12):2052-2062. doi: 10.1002/2211-5463.12741. Epub 2019 Nov 15.

Abstract

Tumor-derived extracellular vesicles (EVs) and their contents are involved in the development of human malignancies. Circular RNAs (circRNAs), enriched in EVs, can regulate diverse cellular processes by acting as microRNA (miRNA) sponges or through other mechanisms. In the present study, we explored the potential roles of circRNAs in EVs in the development of pancreatic ductal adenocarcinoma (PDAC). First, plasma was obtained from patients with PDAC (n = 8) and healthy volunteers (n = 8), and EVs were isolated by the ultracentrifugation method. Nanoparticle tracking analysis and transmission electron microscopy confirmed the size and form of the isolated EVs. The circRNA expression profiles of EVs were investigated by high-throughput whole transcriptome sequencing. We then further validated the accuracy of the circRNA sequencing data by quantitative real-time PCR analysis using plasma samples and PC cell lines, and subsequently performed bioinformatics analysis to reveal the potential functional roles of the differentially expressed circRNAs and to construct a circRNA-miRNA interaction network to predict the target miRNAs of these circRNAs. Our work provides novel targets for further studies concerning the pathogenesis of PDAC.

Keywords: circular RNA; extracellular vesicles; microRNA; pancreatic ductal adenocarcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / blood
  • Adenocarcinoma / genetics
  • Adult
  • Carcinoma, Pancreatic Ductal / blood
  • Carcinoma, Pancreatic Ductal / genetics*
  • Cell Line, Tumor
  • Computational Biology / methods
  • Extracellular Vesicles / genetics*
  • Female
  • Gene Expression Profiling / methods
  • Humans
  • Male
  • MicroRNAs / genetics
  • Pancreatic Neoplasms / blood
  • Pancreatic Neoplasms / genetics
  • RNA, Circular / analysis
  • RNA, Circular / blood
  • RNA, Circular / genetics*
  • Real-Time Polymerase Chain Reaction / methods
  • Transcriptome / genetics

Substances

  • MicroRNAs
  • RNA, Circular