The physiological role of microRNAs (miRNAs) is widely appreciated as a fine-tuner to post-transcriptionally regulate the expression of multiple genes in the cells of origin. Here, we highlight two significant characteristics of miRNAs: (1) they are secreted from the producing cells, and (2) they can deliver the gene silencing signals between living cells in vitro and in vivo. The circulation of miRNAs in human body fluids can be provided with a logical explanation by our discovery that the release of miRNAs is actively controlled through a ceramide-dependent machinery associated with exosome secretion. This finding can contribute to the development of circulating miRNAs as diagnostic biomarkers for a variety of diseases. We also demonstrated that secretory miR-16 was transferred into prostate cancer PC-3M cells subcutaneously xenografted in nude mice, resulting in the suppression of its target gene. This result suggests that faithfully to their primary role, secretory miRNAs can function as a translational inhibitor in recipient cells as well. In conclusion, miRNAs are liberated from their incipient cells, whereby they can exert their full potentials as a silence master of gene expressions.
N Kosaka, H Iguchi, Y Yoshioka, F Takeshita, Y Matsuki, T Ochiya. Secretory mechanisms and intercellular transfer of microRNAs in living cells. J Biol Chem 2010; 285: 17442- 52.
PMID: 20353945 DOI: 10.1074/jbc.M110.107