Pediatric brain tumor cell lines exhibit miRNA-depleted, Y RNA-enriched extracellular vesicles
- 05.01.2022
- Laboratory Investigation
Erschienen in:
- Verfasst von
- Setty M. Magaña
- Timothy E. Peterson
- Jared E. Evans
- Paul A. Decker
- Vernadette Simon
- Jeanette E. Eckel-Passow
- David J. Daniels
- Ian F. Parney
- Erschienen in
- Journal of Neuro-Oncology | Ausgabe 2/2022
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.
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- Titel
- Pediatric brain tumor cell lines exhibit miRNA-depleted, Y RNA-enriched extracellular vesicles
- Verfasst von
-
Setty M. Magaña
Timothy E. Peterson
Jared E. Evans
Paul A. Decker
Vernadette Simon
Jeanette E. Eckel-Passow
David J. Daniels
Ian F. Parney
- Publikationsdatum
- 05.01.2022
- Verlag
- Springer US
- Erschienen in
-
Journal of Neuro-Oncology / Ausgabe 2/2022
Print ISSN: 0167-594X
Elektronische ISSN: 1573-7373 - DOI
- https://doi.org/10.1007/s11060-021-03914-4
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