title: MicroRNAs bind to Toll-like receptors to induce prometastatic inflammatory response.
abstract: MicroRNAs (miRNAs) are small noncoding RNAs, 19-24 nucleotides in length, that regulate gene expression and are expressed aberrantly in most types of cancer. MiRNAs also have been detected in the blood of cancer patients and can serve as circulating biomarkers. It has been shown that secreted miRNAs within exosomes can be transferred from cell to cell and can regulate gene expression in the receiving cells by canonical binding to their target messenger RNAs. Here we show that tumor-secreted miR-21 and miR-29a also can function by another mechanism, by binding as ligands to receptors of the Toll-like receptor (TLR) family, murine TLR7 and human TLR8, in immune cells, triggering a TLR-mediated prometastatic inflammatory response that ultimately may lead to tumor growth and metastasis. Thus, by acting as paracrine agonists of TLRs, secreted miRNAs are key regulators of the tumor microenvironment. This mechanism of action of miRNAs is implicated in tumor-immune system communication and is important in tumor growth and spread, thus representing a possible target for cancer treatment.
authors: Department of Molecular Virology, The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210, USA. mfabbri@chla.usc.edu
authors: Muller
authors: M
authors: Fabbri
authors: Alessio
authors: A
authors: Paone
authors: Federica
authors: F
authors: Calore
authors: Roberta
authors: R
authors: Galli
authors: Eugenio
authors: E
authors: Gaudio
authors: Ramasamy
authors: R
authors: Santhanam
authors: Francesca
authors: F
authors: Lovat
authors: Paolo
authors: P
authors: Fadda
authors: Charlene
authors: C
authors: Mao
authors: Gerard J
authors: GJ
authors: Nuovo
authors: Nicola
authors: N
authors: Zanesi
authors: Melissa
authors: M
authors: Crawford
authors: Gulcin H
authors: GH
authors: Ozer
authors: Dorothee
authors: D
authors: Wernicke
authors: Hansjuerg
authors: H
authors: Alder
authors: Michael A
authors: MA
authors: Caligiuri
authors: Patrick
authors: P
authors: Nana-Sinkam
authors: Danilo
authors: D
authors: Perrotti
authors: Carlo M
authors: CM
authors: Croce
mesh_terms: D000818:Animals; D057809:HEK293 Cells; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000097:blood* / Q000235:genetics / Q000473:pathology / Q000628:therapy; D019899:Paracrine Communication / Q000235:genetics; D012334:RNA, Neoplasm / Q000097:blood* / Q000235:genetics; D051199:Toll-Like Receptor 7 / Q000235:genetics / Q000378:metabolism*; D051200:Toll-Like Receptor 8 / Q000235:genetics / Q000378:metabolism*
chemical_list: C524940:MIRN21 microRNA, human; C531950:MIRN21 microRNA, mouse; C547014:MIRN29 microRNA, mouse; C532045:MIRN29a microRNA, human; D008562:Membrane Glycoproteins; D035683:MicroRNAs; D012334:RNA, Neoplasm; C495348:TLR7 protein, human; C495349:TLR8 protein, human; C552579:TLR8 protein, mouse; C477038:Tlr7 protein, mouse; D051199:Toll-Like Receptor 7; D051200:Toll-Like Receptor 8