miRNa signature in small extracellular vesicles and their association with platinum resistance and cancer recurrence in ovarian cancer

Abstract

Carboplatin, administered as a single drug or in combination with paclitaxel, is the standard chemotherapy treatment for patients with ovarian cancer (OVCA). Recent evidence suggests that miRNAs associated with small extracellular vesicles (sEVs) participate in the development of chemoresistance. We studied the effect of carboplatin in a heterogeneity population of OVCA cells and their derived sEVs to identify mechanisms associated with chemoresistance. sEVs were quantified using an engineered superparamagnetic material, gold-loaded ferric oxide nanotubes and a screen-printed electrode. miR-21-3p, miR-21-5p, and miR-891-5p are enriched in sEVs, and they contribute to carboplatin resistance in OVCA. Using a quantitative MS/MS, miR-21-5p activates glycolysis and increases the expression of ATP-binding cassette family and a detoxification enzyme. miR-21-3p and miR-891-5p increase the expression of proteins involved in DNA repair mechanisms. Interestingly, the levels of miR-891-5p within sEVs are significantly higher in patients at risk of ovarian cancer relapse. Identification of miRNAs in sEVs also provides the opportunity to track them in biological fluids to potentially determine patient response to chemotherapy.