Dados do Resumo

Título

Extracellular Vesicle-Packaged miR-495-3 and miR-485-5p impair proliferation and migration in thyroid carcinoma

Introdução

Thyroid cancer (TC) has become the most frequently diagnosed malignancy in the endocrine system in recent years. Recently, Extracellular Vesicles (EVs) have been identified as a promising delivery system for microRNAs (miRs) and drugs. However, the potential of exosomal-miRs to offer new therapeutic targets for TC remains not explored.

Objetivo

We aimed to evaluate the role of EVs as a delivery system for tumor-suppressor miRNAs in TC.

Métodos

Herein, we hypothesized that normal thyroid follicular cells (NThy-ORI) overexpressing miR-485-5p/miR-495-3p could produce EVs enriched with these miRs and influence oncogenic pathways through their delivery. EVs enriched with tumor-suppressor miRs were isolated by differential ultracentrifugation. NTA and EM were employed to determine the size and morphology of the EVs. We used in vitro assays to further understand the impact of EVs-miRs on the tumorigenic process of TC.

Resultados

First, the expression of miRs miR-495 and miR-485 was evaluated in non-tumoral cell lines (NThy-ORI) and TC cell lines, TPC-1, BCPAP, and KTC-2, with decreased expression in TC cells. Then, we show that miR-495 and miR-485 are released to a conditioned medium (CM) and also enveloped in EVs and that these molecules are transferred to tumor cells. EVs enriched with miRNAs impaired proliferation and migration.

Conclusões

So far, our results suggest that EVs enriched with tumor suppressor miRNAs miR-495-3p and miR-485-5p from non-tumoral cells can deliver these miRNAs to cancer cells and impair important pathways related to tumorigenesis. Further, other functional assays are necessary to characterize the therapeutic potential of this strategy.

Financiador do resumo

CNPq (140227/2021-0)

Palavras Chave

Extracellular Vesicles; miRNAs; Thyroid Cancer