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


  • A. Buonfiglioli
  • I.E. Efe
  • D. Guneykaya
  • A. Ivanov
  • Y. Huang
  • E. Orlowski
  • C. Krüger
  • R.A. Deisz
  • D. Markovic
  • C. Flüh
  • A.G. Newman
  • U.C. Schneider
  • D. Beule
  • S.A. Wolf
  • O. Dzaye
  • D.H. Gutmann
  • M. Semtner
  • H. Kettenmann
  • S. Lehnardt


  • Cell Reports


  • Cell Rep 29 (11): 3460-3471


  • 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.