MicroRNA-Mediated Dynamic Bidirectional Shift between the Subclasses of Glioblastoma Stem-like Cells

• Main Authors: Arun K. Rooj, Franz Ricklefs, Marco Mineo, Ichiro Nakano, E. Antonio Chiocca, Agnieszka Bronisz, Jakub Godlewski
• Format: Article
• Language: English
• Published: Elsevier 2017-06-01
• Series: Cell Reports
• Subjects: glioblastoma; microRNA; Polycomb repressive complex; stem cells; subtype transition; heterogeneity; chromatin; non-coding RNA; exosomes
• Online Access: http://www.sciencedirect.com/science/article/pii/S2211124717306824

Large-scale transcriptomic profiling of glioblastoma (GBM) into subtypes has provided remarkable insight into the pathobiology and heterogeneous nature of this disease. The mechanisms of speciation and inter-subtype transitions of these molecular subtypes require better characterization to facilitate the development of subtype-specific targeting strategies. The deregulation of microRNA expression among GBM subtypes and their subtype-specific targeting mechanisms are poorly understood. To reveal the underlying basis of microRNA-driven complex subpopulation dynamics within the heterogeneous intra-tumoral ecosystem, we characterized the expression of the subtype-enriched microRNA-128 (miR-128) in transcriptionally and phenotypically diverse subpopulations of patient-derived glioblastoma stem-like cells. Because microRNAs are capable of re-arranging the molecular landscape in a cell-type-specific manner, we argue that alterations in miR-128 levels are a potent mechanism of bidirectional transitions between GBM subpopulations, resulting in intermediate hybrid stages and emphasizing highly intricate intra-tumoral networking.