Exosome-Derived miR21 Elicits an Epithelial Ovarian Cancer Cell-Promoted Phenotype

Abstract

Background: The purpose of this study was to identify how exosome-derived miR21 affected epithelial ovarian cancer (EOC) cells. Methods: miR21 expression was examined in isolated-exosomes of human normal ovarian epithelial cell line IOSE-80 and EOC cell line SKOV-3. The exosomes morphology was evaluated via a transmission electron microscopy. SKOV-3 cells were transfected with miR21 mimic or inhibitor, and then the transfected cell-secreted exosomes were co-cultured with untransfected cells. The quantitative real time-polymerase chain reaction (qRT-PCR) was used to analyze the miR21 expression in cells and exosomes derived from cells. The exosome-treated cells proliferation, apoptosis, migration and invasion were measured by performing methyl thiazolyl tetrazolium (MTT) assay, colony formation assay, flow cytometry, wound-healing assay, and transwell assay, respectively. The exosome molecular markers expression and epithelial-mesenchymal transition (EMT)-related proteins expression were examined via the Western blot analysis. Results: SKOV-3 cells had prominently significantly higher exosomal miR21 expression than IOSE-80 cells. Reduced exosomal miR21 expression led to a significant decrease in miR21 expression in exosome-treated SKOV-3 cells, while exosomal miR21 overexpression significantly increased miR21 expression. Overexpression of miR21 in exosomes significantly promoted ovarian cancer cell proliferation, suppressed cell apoptosis, facilitated the invasion and migration, and regulated the EMT-related protein expression, while down-regulated miR21 expression in exosomes showed significant counterproductive effects. Conclusions: This study found that EOC cell-derived exosomal miR21 could enhanced EOC cells proliferation, migration, and invasion while inhibiting apoptosis, suggesting that exosomal miR21 may be a tumor promotor for ovarian cancer.