Shift of microRNA profile upon orthotopic xenografting of glioblastoma spheroid cultures
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- 作者：Bo Halle ; Mads Thomassen ; Ranga Venkatesan ; Vivek Kaimal…
- 刊名：Journal of Neuro-Oncology
- 出版年：2016
- 出版时间：July 2016
- 年：2016
- 卷：128
- 期：3
- 页码：395-404
- 全文大小：9,977 KB
- 刊物类别：Medicine
- 刊物主题：Medicine & Public Health
Oncology - 出版者：Springer Netherlands
- ISSN：1573-7373
- 卷排序：128
文摘
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.KeywordsMicroRNAGlioblastomaTumor stem cellCancer stem cell