Role of Non-Coding RNAs in Cancer

MicroRNAs (miRNAs) are small non-coding RNAs, 19-24 nucleotides in length, which regulate gene expression, and are aberrantly expressed in most types of cancer. MiRNAs have also 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 can also function by a novel mechanism, by binding as ligands to receptors of the Toll-like receptor family, murine TLR7 and human TLR8, in immune cells, triggering a TLR-mediated prometastatic inflammatory response, which ultimately may lead to tumor growth, spreading and metastasis. Thus, by acting as peregrine agonists of TLRs, secreted miRNAs are key regulators of the tumor microenvironment. This mechanism of action of miRNAs is implicated in the tumor-immune system communication, and is important in tumor growth and spread, therefore representing a new possible target for cancer treatment.