Platelet microparticle-mediated transfer of miR-939 to epithelial ovarian cancer cells promotes epithelial to mesenchymal transition

Abstract

Epithelial ovarian cancer (EOC) patients frequently suffer from thrombocytosis, which leads to a poor prognosis. However, the mechanism underlying platelet regulation of biological behavior in EOC remains unclear. The associations between clinicopathological characteristics and thrombocytosis in 171 EOC patients were studied, preoperative thrombocytosis was significantly associated with the stage, metastasis scope, level of preoperative CA125 and overall survival. When SKOV3 cells were cocultured with platelet microparticles (PMPs), the expression of molecules associated with epithelial-mesenchymal transition (EMT) was increased. The proliferation and migration of SKOV3 cells were also enhanced. Based on the miRNA microarray of the PMPs derived between thrombin-stimulating and apoptotic platelets, we demonstrated that over-expression or complete knockdown of miR-939 in the SKOV3 cells strengthened or weakened EMT. Secretory phospholipase A2 type IIA (sPLA₂-IIa) has been shown to mediate PMPs intake by SKOV3 cells. The knockdown of sPLA₂-IIa in SKOV3 cells verified that PMPs were involved in crosstalk during the regulation of cancer cells by transferring miRNA. This study revealed an important role for PMPs in the crosstalk of platelets and cancer cells through miR-939 shedding mediated by sPLA₂-IIa, which enables EOC to undergo EMT and enhances cancer progression. Our findings pave the way for developing a novel therapeutic strategy for EOC targets such as PMPs, miR-939 or sPLA₂-IIa.