Rooj Arun K, Ricklefs Franz, Mineo Marco, Nakano Ichiro, Chiocca E Antonio, Bronisz Agnieszka, Godlewski Jakub
Harvey Cushing Neuro-Oncology Laboratories, Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Harvey Cushing Neuro-Oncology Laboratories, Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Department of Neurosurgery, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany.
Cell Rep. 2017 Jun 6;19(10):2026-2032. doi: 10.1016/j.celrep.2017.05.040.
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.
对胶质母细胞瘤（GBM）进行大规模转录组分析以划分亚型，为深入了解该疾病的病理生物学和异质性本质提供了重要线索。这些分子亚型的形成机制和亚型间转变需要更深入的表征，以促进亚型特异性靶向策略的开发。目前对GBM亚型间微小RNA表达失调及其亚型特异性靶向机制了解甚少。为了揭示异质性肿瘤内生态系统中微小RNA驱动的复杂亚群动态变化的潜在基础，我们对患者来源的胶质母细胞瘤干细胞样细胞在转录和表型上不同的亚群中富集于亚型的微小RNA-128（miR-128）的表达进行了表征。由于微小RNA能够以细胞类型特异性方式重新排列分子格局，我们认为miR-128水平的改变是GBM亚群之间双向转变的有效机制，导致中间杂交阶段并强调肿瘤内高度复杂的网络。
