The chimeric aptamer axl-miR-214sponge inhibits breast cancer and melanoma dissemination

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 which 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 evidenced. Instead, expression of ALCAM, a target of the anti-metastatic miR-148b and downstream effector of miR-214, was found decreased. More importantly, 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 evidenced, together with increased cell death in primary tumor masses. No toxicity was evidenced 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.