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11.04.2016 | Laboratory Investigation

Shift of microRNA profile upon orthotopic xenografting of glioblastoma spheroid cultures

verfasst von: Bo Halle, Mads Thomassen, Ranga Venkatesan, Vivek Kaimal, Eric G. Marcusson, Sune Munthe, Mia D. Sørensen, Charlotte Aaberg-Jessen, Stine S. Jensen, Morten Meyer, Torben A. Kruse, Helle Christiansen, Steffen Schmidt, Jan Mollenhauer, Mette K. Schulz, Claus Andersen, Bjarne W. Kristensen

Erschienen in: Journal of Neuro-Oncology | Ausgabe 3/2016

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Abstract

Glioblastomas always recur despite surgery, radiotherapy and chemotherapy. A key player in the therapeutic resistance may be immature tumor cells with stem-like properties (TSCs) escaping conventional treatment. A group of promising molecular targets are microRNAs (miRs). miRs are small non-coding RNAs exerting post-transcriptional regulation of gene expression. In this study we aimed to identify over-expressed TSC-related miRs potentially amenable for therapeutic targeting. We used non-differentiated glioblastoma spheroid cultures (GSCs) containing TSCs and compared these to xenografts using a NanoString nCounter platform. This revealed 19 over-expressed miRs in the non-differentiated GSCs. Additionally, non-differentiated GSCs were compared to neural stem cells (NSCs) using a microarray platform. This revealed four significantly over-expressed miRs in the non-differentiated GSCs in comparison to the NSCs. The three most over-expressed miRs in the non-differentiated GSCs compared to xenografts were miR-126, -137 and -128. KEGG pathway analysis suggested the main biological function of these over-expressed miRs to be cell-cycle arrest and diminished proliferation. To functionally validate the profiling results suggesting association of these miRs with stem-like properties, experimental over-expression of miR-128 was performed. A consecutive limiting dilution assay confirmed a significantly elevated spheroid formation in the miR-128 over-expressing cells. This may provide potential therapeutic targets for anti-miRs to identify novel treatment options for GBM patients.

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Titel: Shift of microRNA profile upon orthotopic xenografting of glioblastoma spheroid cultures
verfasst von: Bo Halle
Mads Thomassen
Ranga Venkatesan
Vivek Kaimal
Eric G. Marcusson
Sune Munthe
Mia D. Sørensen
Charlotte Aaberg-Jessen
Stine S. Jensen
Morten Meyer
Torben A. Kruse
Helle Christiansen
Steffen Schmidt
Jan Mollenhauer
Mette K. Schulz
Claus Andersen
Bjarne W. Kristensen
Publikationsdatum: 11.04.2016
Verlag: Springer US
Erschienen in: Journal of Neuro-Oncology / Ausgabe 3/2016
Print ISSN: 0167-594X
Elektronische ISSN: 1573-7373
DOI: https://doi.org/10.1007/s11060-016-2125-x

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