Abstract
MicroRNAs (miRNAs) are often deregulated in cancer. We previously showed that inhibition of the pro-metastatic miR-214 strongly impairs tumor dissemination. We recently developed a chimeric aptamer, axl-miR-214sponge, including an oligonucleotide sequence able to inhibit miR-214 (miR-214sponge) linked to GL21.T (axl), an aptamer that binds specifically to axl, an oncogenic tyrosine kinase receptor abundantly expressed on various malignant melanoma and breast cancer cells. When axl-positive but not axl-negative cancer cells were treated with axl-miR-214sponge, reduced migration, invasion, and transendothelial migration were observed. In parallel, augmented levels of two miR-214 direct targets, TFAP2C and ITGA3, were seen. Instead, expression of ALCAM, a target of the anti-metastatic miR-148b and downstream effector of miR-214, was found to be decreased. More important, when mice carrying xenotransplants derived from triple-negative breast cancer or melanoma cells were treated in loco or systemically with the axl-miR-214sponge conjugates, reduced cancer dissemination was seen, together with increased cell death in primary tumor masses. No toxicity was noted in animals. In summary, our data suggest that axl-miR-214sponge is specific, effective, and safe in blocking axl-positive cancer cell spreading. Thus, it represents a promising targeted therapy tool to fight metastasis.