A new role for microRNAs, as ligands of Toll-like receptors

RNA Biol. 2013 Feb;10(2):169-74. doi: 10.4161/rna.23144. Epub 2013 Jan 7.


Tumor microenvironment plays a central role in the development and dissemination of cancer cells. In addition to study each specific cellular component of the microenvironment, it has become clear that it is the type and amount of information that cells exchange that ultimately affects cancer phenotype. Recently, it has been discovered that intercellular communication occurs through the release of microvesicles and exosomes, whose cargo represents the information released by one cell to a recipient cell. A key component of this cargo is represented by microRNAs (miRNAs), small non-coding RNAs with gene regulatory functions. We discovered that miRNAs released by cancer cells within microvesicles can reach and bind to Toll-like receptors (TLRs) in surrounding immune cells, and activate them in a paracrine loop. As a result, immune cells produce cytokines that increase cell proliferation and metastatic potential. This discovery provides the rationale for the development of new drugs that might be used in the treatment of cancer as well as other inflammation-related diseases.

Keywords: IL-6; TNF-α; Toll-like receptors; exosomes; metastasis; microRNAs; tumor microenvironment.

MeSH terms

  • Animals
  • Biomarkers, Tumor / immunology
  • Biomarkers, Tumor / metabolism
  • Cell Communication
  • Cell Proliferation
  • Cytokines / immunology
  • Exosomes
  • Humans
  • Inflammation / genetics*
  • Inflammation / immunology
  • Ligands
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neoplasms / genetics
  • Neoplasms / immunology
  • Neoplasms / metabolism
  • RNA, Neoplasm / genetics
  • RNA, Neoplasm / metabolism*
  • Toll-Like Receptors / genetics
  • Toll-Like Receptors / immunology
  • Toll-Like Receptors / metabolism*
  • Transcription, Genetic
  • Tumor Microenvironment*


  • Biomarkers, Tumor
  • Cytokines
  • Ligands
  • MicroRNAs
  • RNA, Neoplasm
  • Toll-Like Receptors