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let-7 microRNAs regulate microglial function and suppress glioma growth through Toll-like receptor 7

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Item Type:Article
Title:let-7 microRNAs regulate microglial function and suppress glioma growth through Toll-like receptor 7
Creators Name:Buonfiglioli, A. and Efe, I.E. and Guneykaya, D. and Ivanov, A. and Huang, Y. and Orlowski, E. and Krüger, C. and Deisz, R.A. and Markovic, D. and Flüh, C. and Newman, A.G. and Schneider, U.C. and Beule, D. and Wolf, S.A. and Dzaye, O. and Gutmann, D.H. and Semtner, M. and Kettenmann, H. and Lehnardt, S.
Abstract:Microglia express Toll-like receptors (TLRs) that sense pathogen- and host-derived factors, including single-stranded RNA. In the brain, let-7 microRNA (miRNA) family members are abundantly expressed, and some have recently been shown to serve as TLR7 ligands. We investigated whether let-7 miRNA family members differentially control microglia biology in health and disease. We found that a subset of let-7 miRNA family members function as signaling molecules to induce microglial release of inflammatory cytokines, modulate antigen presentation, and attenuate cell migration in a TLR7-dependent manner. The capability of the let-7 miRNAs to control microglial function is sequence specific, mapping to a let-7 UUGU motif. In human and murine glioblastoma/glioma, let-7 miRNAs are differentially expressed and reduce murine GL261 glioma growth in the same sequence-specific fashion through microglial TLR7. Taken together, these data establish let-7 miRNAs as key TLR7 signaling activators that serve to regulate the diverse functions of microglia in health and glioma.
Keywords:Glioblastoma, Lethal-7, Microglia, MicroRNA, Toll-Like Receptor 7, Animals, Mice, Rats
Source:Cell Reports
ISSN:2211-1247
Publisher:Cell Press / Elsevier
Volume:29
Number:11
Page Range:3460-3471
Date:10 December 2019
Official Publication:https://doi.org/10.1016/j.celrep.2019.11.029
PubMed:View item in PubMed

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