Details

Autor(en) / Beteiligte

• Buonfiglioli, Alice
• Efe, Ibrahim E.
• Guneykaya, Dilansu
• Ivanov, Andranik
• Huang, Yimin
• Orlowski, Elisabeth
• Krüger, Christina
• Deisz, Rudolf A.
• Markovic, Darko
• Flüh, Charlotte
• Newman, Andrew G.
• Schneider, Ulf C.
• Beule, Dieter
• Wolf, Susanne A.
• Dzaye, Omar
• Gutmann, David H.
• Semtner, Marcus
• Kettenmann, Helmut
• Lehnardt, Seija

Titel

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

Ist Teil von

• Cell reports (Cambridge), 2019-12, Vol.29 (11), p.3460-3471.e7

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2019

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• 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. [Display omitted] •let-7 miRNAs act as Toll-like receptor (TLR) 7 signaling molecules in glioma•Extracellular let-7 miRNAs differentially modulate microglial biology•The sequence motif UUGU is responsible for let-7-induced microglial activation•Select let-7 miRNAs attenuate glioma growth by directly activating microglial TLR7 Buonfiglioli et al. elucidate the role of let-7 miRNAs acting as Toll-like receptor (TLR) ligands in the brain. Select let-7 miRNAs function as signaling molecules to modulate diverse microglial functions and glioma growth through TLR7. These data establish let-7 miRNAs as TLR7 signaling activators of microglia in health and glioma.