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

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.; Lehnardt, S.

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:	Buonfiglioli, A. ORCID: https://orcid.org/0000-0002-5550-9360, Efe, I.E. ORCID: https://orcid.org/0000-0002-4232-3305, Guneykaya, D., Ivanov, A. ORCID: https://orcid.org/0000-0002-4824-1925, Huang, Y. ORCID: https://orcid.org/0000-0001-9600-1195, Orlowski, E., Krüger, C., Deisz, R.A., Markovic, D., Flüh, C., Newman, A.G. ORCID: https://orcid.org/0000-0002-0222-9162, Schneider, U.C., Beule, D. ORCID: https://orcid.org/0000-0002-3284-0632, Wolf, S.A. ORCID: https://orcid.org/0000-0003-0922-8418, Dzaye, O., Gutmann, D.H. ORCID: https://orcid.org/0000-0002-3127-5045, Semtner, M. ORCID: https://orcid.org/0000-0001-9379-9023, Kettenmann, H. ORCID: https://orcid.org/0000-0001-8208-0291 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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