Transfer of microRNA via Macrophage-Derived Extracellular Vesicles Promotes Proneural-to-Mesenchymal Transition in Glioma Stem Cells

Menée in vitro et à l'aide d'une xénogreffe sur un modèle murin, cette étude met en évidence un mécanisme par lequel les vésicules extracellulaires dérivées des macrophages, en transférant certains microARNs aux cellules souches de gliome, favorisent l'évolution d'un gliome proneural vers une forme mésenchymateuse

Résumé en anglais

Proneural-to-mesenchymal transition (PMT) is a common process in glioblastoma (GBM) progression that leads to increased radiotherapy resistance. However, the mechanism underlying PMT is poorly understood. Here, we found that tumor-associated macrophages (TAMs) triggered PMT in glioma stem cells (GSCs) via small extracellular vesicles (sEVs). sEVs from monocyte-derived macrophages transferred miR-27a-3p, miR-22-3p and miR-221-3p to GSCs, and these microRNAs (miRs) promoted several mesenchymal (MES) phenotypes in proneural(PN) GSCs by simultaneously targeting CHD7. We found that CHD7 played a critical role in the maintenance of the PN phenotype and CHD7 knockdown significantly promoted PMT in GSCs via the RelB/P50 and p-STAT3 pathways. The induction of PMT by sEVs containing miR-27a-3p, miR-22-3p and miR-221-3p in a xenograft nude mouse model exacerbated radiotherapy resistance and thus decreased the benefits of radiotherapy. Collectively, these findings identified macrophage-derived sEVs (MDEs) as key regulators of PMT in GSCs and demonstrated that CHD7 is a novel inhibitor of PMT.