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

Publication date: 6 June 2017
Source:Cell Reports, Volume 19, Issue 10
Author(s): Arun K. Rooj, Franz Ricklefs, Marco Mineo, Ichiro Nakano, E. Antonio Chiocca, Agnieszka Bronisz, Jakub Godlewski
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.

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Rooj et al. find that miR-128-dependent transitions between heterogeneous GSC subtypes lead to molecular rearrangements influencing GSC phenotypes in vitro and in vivo. These transcriptomic transitions, mediated largely by Polycomb repressive complexes, are predictive of GBM patient subtype identity and outcome.


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