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

Cell Reports

Ichiro Nakano¹  Arun K. Rooj²  Franz Ricklefs²  Agnieszka Bronisz²  E. Antonio Chiocca²  Jakub Godlewski²  Marco Mineo² 

[1] Department of Neurosurgery and Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL 35243, USA;Harvey Cushing Neuro-Oncology Laboratories, Department of Neurosurgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA;

关键词: glioblastoma;    microRNA;    Polycomb repressive complex;    stem cells;    subtype transition;    heterogeneity;    chromatin;    non-coding RNA;    exosomes;   

DOI  :  10.1016/j.celrep.2017.05.040

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown