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

## TL;DR

A new chimeric aptamer called axl-miR-214sponge was shown to block the spread of breast cancer and melanoma in mice without causing toxicity.

## Contribution

The development and testing of a novel chimeric aptamer that targets both miR-214 and the AXL receptor to inhibit cancer metastasis.

## Key findings

- Axl-miR-214sponge reduced migration, invasion, and transendothelial migration in axl-positive cancer cells.
- Systemic administration of axl-miR-214sponge reduced cancer dissemination in mice without toxicity.
- The treatment increased levels of TFAP2C and ITGA3 while decreasing ALCAM expression in cancer cells.

## 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.

Systemic administration of the chimeric aptamer axl-miR-214sponge, formed by an oligonucleotide sequence able to inhibit miR-214 (miR-214sponge) linked to an aptamer (GL21.T) able to specifically bind the oncogenic receptor axl, was proven to reduce cancer cell dissemination in mice carrying breast cancer or melanoma cell-derived xenotransplants without toxicity signs.