| Literature DB >> 32350000 |
Xing Guo1,2,3, Gang Li1,2,3, Zongpu Zhang4,2,3, Jianye Xu4,2,3, Zihang Chen4,2,3, Huizhi Wang4,2,3, Hao Xue4,2,3, Chunlei Yang4,2,3, Qindong Guo4,2,3, Yanhua Qi4,2,3, Xiaofan Guo4,2,3, Mingyu Qian4,2,3, Shaobo Wang4,2,3, Wei Qiu4,2,3, Xiao Gao4,2,3, Rongrong Zhao4,2,3.
Abstract
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 triggered PMT in glioma stem cells (GSC) via small extracellular vesicles (sEV). sEVs from monocyte-derived macrophages transferred miR-27a-3p, miR-22-3p, and miR-221-3p to GSCs, and these miRNAs promoted several mesenchymal 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 as key regulators of PMT in GSCs and demonstrated that CHD7 is a novel inhibitor of PMT. ©2020 American Association for Cancer Research.Entities:
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Year: 2020 PMID： 32350000 DOI： 10.1158/2326-6066.CIR-19-0759
Source DB: PubMed Journal: Cancer Immunol Res ISSN： 2326-6066 Impact factor: 11.151