Pediatric brain tumor cell lines exhibit miRNA-depleted, Y RNA-enriched extracellular vesicles

Setty M. Magaña, Timothy E. Peterson, Jared E. Evans, Paul A. Decker, Vernadette Simon, Jeanette E. Eckel-Passow, David Daniels, Ian F. Parney

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Medulloblastoma (MB) and diffuse infiltrative pontine glioma (DIPG) are malignant pediatric tumors. Extracellular vesicles (EVs) and their bioactive cargoes have been implicated in tumorigenesis. Most studies have focused on adult tumors, therefore the role of EVs and the noncoding RNA (ncRNA) landscape in pediatric brain tumors is not fully characterized. The overall aim of this pilot study was to isolate EVs from MB and DIPG patient-derived cell lines and to explore the small ncRNA transcriptome. Methods: EVs from 3 DIPG and 4 MB patient-derived cell lines were analyzed. High-throughput next generation sequencing interrogated the short non-coding RNA (ncRNA) transcriptome. Known and novel miRNAs were quantified. Differential expression analysis, in silico target prediction, and functional gene enrichment were performed. Results: EV secretomes from MB and DIPG patient-derived cell lines demonstrated discrete ncRNA biotypes. Notably, miRNAs were depleted and Y RNAs were enriched in EV samples. Hierarchical cluster analysis revealed high discrimination in miRNA expression between DIPG and MB cell lines and RNA-Seq identified novel miRNAs not previously implicated in MB or DIPG pathogenesis. Known and putative target genes of dysregulated miRNAs were identified. Functional annotation analysis of the target genes for differentially expressed EV-and parental-derived miRNAs revealed significant cancer-related pathway involvement. Conclusions: This hypothesis-generating study demonstrated that pediatric brain tumor-derived cell lines secrete EVs comprised of various ncRNA cargoes. Validation of these findings in patient samples may provide new insights into the pediatric brain tumor microenvironment and identification of novel therapeutic candidates.

Original languageEnglish (US)
Pages (from-to)269-279
Number of pages11
JournalJournal of neuro-oncology
Volume156
Issue number2
DOIs
StatePublished - Jan 2022

Keywords

  • Deep sequencing
  • Extracellular vesicles
  • Noncoding RNA
  • Pediatric brain tumors
  • miRNA

ASJC Scopus subject areas

  • Oncology
  • Neurology
  • Clinical Neurology
  • Cancer Research

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