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Item Type: | Article |
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Title: | let-7 microRNAs regulate microglial function and suppress glioma growth through Toll-like receptor 7 |
Creators Name: | Buonfiglioli, A., Efe, I.E., Guneykaya, D., Ivanov, A., Huang, Y., Orlowski, E., Krüger, C., Deisz, R.A., Markovic, D., Flüh, C., Newman, A.G., Schneider, U.C., Beule, D., Wolf, S.A., Dzaye, O., Gutmann, D.H., Semtner, M., 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 |
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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