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

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

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

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.

Original languageEnglish
Pages (from-to)3460-3471.e7
JournalCell Reports
Volume29
Issue number11
DOIs
StatePublished - Dec 10 2019

Keywords

  • Toll-like receptor 7
  • glioblastoma
  • lethal-7
  • microRNA
  • microglia

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