We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Shift of microRNA profile upon orthotopic xenografting of glioblastoma spheroid cultures.
- Authors
Halle, Bo; Thomassen, Mads; Venkatesan, Ranga; Kaimal, Vivek; Marcusson, Eric; Munthe, Sune; Sørensen, Mia; Aaberg-Jessen, Charlotte; Jensen, Stine; Meyer, Morten; Kruse, Torben; Christiansen, Helle; Schmidt, Steffen; Mollenhauer, Jan; Schulz, Mette; Andersen, Claus; Kristensen, Bjarne
- 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.
- Subjects
GLIOBLASTOMA multiforme treatment; GLIOBLASTOMA multiforme; ONCOLOGIC surgery; CANCER radiotherapy; CANCER chemotherapy; MICRORNA; PATIENTS; GENETICS
- Publication
Journal of Neuro-Oncology, 2016, Vol 128, Issue 3, p395
- ISSN
0167-594X
- Publication type
Article
- DOI
10.1007/s11060-016-2125-x