let-7 MicroRNAs Regulate Microglial Function and Suppress Glioma Growth through Toll-Like Receptor 7.

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.

• Authors: Alice Buonfiglioli, Ibrahim E Efe, Dilansu Guneykaya, Andranik Ivanov, Yimin Huang, Elisabeth Orlowski, Christina Krüger, Rudolf A Deisz, Darko Markovic, Charlotte Flüh, Andrew G Newman, Ulf C Schneider, Dieter Beule, Susanne A Wolf, Omar Dzaye, David H Gutmann, Marcus Semtner, Helmut Kettenmann, Seija Lehnardt
• Journal: Cell reports (Cell Rep) Vol. 29 Issue 11 Pg. 3460-3471.e7 (Dec 10 2019) ISSN: 2211-1247 [Electronic] United States
• PMID: 31825829 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.

Chemical References

• MicroRNAs
• TLR7 protein, human
• Toll-Like Receptor 7
• mirnlet7 microRNA, human

Topics

• Animals
• Brain Neoplasms (genetics, metabolism, pathology)
• Cell Line, Tumor
• Cells, Cultured
• Female
• Gene Expression Regulation, Neoplastic
• Glioma (genetics, metabolism, pathology)
• Humans
• Male
• Mice
• Mice, Inbred C57BL
• MicroRNAs (genetics, metabolism)
• Microglia (metabolism)
• Signal Transduction
• Toll-Like Receptor 7 (genetics, metabolism)