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- Tüzesi, Ágota, 1982
(author)
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Epigenetics of paediatric glioma stem cells; focusing on exosomes, miRNAs and DNA methylation
- 2019
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Doctoral thesis (other academic/artistic)abstract
- Tumours in the central nervous system are accountable for the majority of cancer-related deaths in children. Glioblastoma multiforme, one of the deadliest of the central nervous system tumours, is partly driven by glioma stem cells. The generation and maintenance of these cells is orchestrated by complex genetic and epigenetic mechanisms. This thesis investigates the role of two epigenetic players, miRNAs and DNA methylation, as well as the involvement of exosomes in paediatric glioma stem cells. The first study profiles the miRNA content of these cells and compares it to normal neural stem cells. Furthermore, the miRNA content of the exosomes secreted by glioma stem cells and its effect on normal stem cells is determined. The second study investigates how specific miRNAs are regulated and how they could potentially influence glioma stem cells’ response to the chemotherapeutic agent temozolomide. These studies provide new insights into the multifaceted epigenetic regulation of glioma stem cells. The gained knowledge could lead to a better understanding of the biological processes behind brain tumours.
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| 2. |
- Tüzesi, Ágota, 1982, et al.
(author)
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Pediatric brain tumor cells release exosomes with a miRNA repertoire that differs from exosomes secreted by normal cells
- 2017
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In: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 8:52, s. 90164-90175
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Journal article (peer-reviewed)abstract
- High-grade gliomas (HGGs) are very aggressive brain tumors with a cancer stem cell component. Cells, including cancer stem cells, release vesicles called exosomes which contain small non-coding RNAs such as microRNAs (miRNAs). These are thought to play an important role in cell-cell communication. However, we have limited knowledge of the types of exosomal miRNAs released by pediatric HGG stem cells; a prerequisite for exploring their potential roles in HGG biology. Here we isolated exosomes released by pediatric glioma stem cells (GSCs) and compared their repertoire of miRNAs to genetically normal neural stem cells (NSCs) exosomes, as well as their respective cellular miRNA content. Whereas cellular miRNAs are similar, we find that the exosomal miRNA profiles differ between normal and tumor cells, and identify several differentially expressed miRNAs. Of particular interest is miR-1290 and miR-1246, which have previously been linked to 'stemness' and invasion in other cancers. We demonstrate that GSC-secreted exosomes influence the gene expression of receiving NSCs, particularly targeting genes with a role in cell fate and tumorigenesis. Thus, our study shows that GSCs and NSCs have similar cellular miRNA profiles, yet differ significantly in the repertoire of exosomal miRNAs and these could influence malignant features of HGG. © Tuzesi et al.
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