Identification of Dysregulated microRNAs in Glioblastoma Stem-like Cells

Identification of Dysregulated microRNAs in Glioblastoma Stem-like Cells

Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor in adults. Despite multimodal therapy, median survival is poor at 12–15 months. At the molecular level, radio-/chemoresistance and resulting tumor progression are attributed to a small fraction of tumor cells, termed glio...

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Autoren: Evers, Lara, Schäfer, Agnes, Pini, Raffaella, Zhao, Kai, Stei, Susanne, Nimsky, Christopher, Bartsch, Jörg W.
Format: Artikel
Sprache:Englisch
Veröffentlicht: Philipps-Universität Marburg 2023
Schlagworte:
glioblastoma stem-like cells
miR-425-5p
let-7
GFAP
microRNA
glioblastoma multiforme
miR-17-5p
differentiation
miR-223-3p
Medizin
Medical sciences Medicine
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Zusammenfassung:Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor in adults. Despite multimodal therapy, median survival is poor at 12–15 months. At the molecular level, radio-/chemoresistance and resulting tumor progression are attributed to a small fraction of tumor cells, termed glioblastoma stem-like cells (GSCs). These CD133-expressing, self-renewing cells display the properties of multi-lineage differentiation, resulting in the heterogenous composition of GBM. MicroRNAs (miRNAs) as regulators of gene expression at the post-transcriptional level can alter many pathways pivotal to cancer stem cell fate. This study explored changes in the miRNA expression profiles in patient-derived GSCs altered on differentiation into glial fiber acid protein (GFAP)-expressing, astrocytic tumor cells using a polymerase chain reaction (PCR) array. Initially, 22 miRNAs showed higher expression in GSCs and 9 miRNAs in differentiated cells. The two most downregulated miRNAs in differentiated GSCs were miR-17-5p and miR-425-5p, whilst the most upregulated miRNAs were miR-223-3p and let-7-5p. Among those, miR-425-5p showed the highest consistency in an upregulation in all three GSCs. By transfection of a 425-5p miRNA mimic, we demonstrated downregulation of the GFAP protein in differentiated patient-derived GBM cells, providing potential evidence for direct regulation of miRNAs in the GSC/GBM cell transition.
Beschreibung:Gefördert durch den Open-Access-Publikationsfonds der UB Marburg.
DOI:10.3390/brainsci13020350

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