Platelet microparticle-mediated transfer of miR-939 to epithelial ovarian cancer cells promotes epithelial to mesenchymal transition
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Meiling Tang1,*, Lu Jiang1,*, Yingying Lin2, Xiaoli Wu1, Kai Wang3, Qizhi He4, Xipeng Wang5 and Weiping Li6
1Department of Gynecology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, China
2Department of Neurosurgery, Renji Hospital, School of Medicine, Shanghai Jiao-Tong University, Shanghai, China
3Central Laboratory, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, China
4Department of Pathology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, China
5Department of Gynecology and Obstetrics, Xinhua Hospital, Affiliated with Shanghai Jiao Tong University, School of Medicine, Shanghai, China
6Department of Obstetrics and Gynecology, Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medcine, Shanghai, China
*These authors have contributed equally to this work
Xipeng Wang, email: [email protected]
Weiping Li, email: [email protected]
Keywords: EOC; PMPs; epithelial - mesenchymal transition (EMT); miR-939; secretary phospholipase A2 type IIA (sPLA2-IIa)
Received: December 08, 2016 Accepted: August 26, 2017 Published: October 27, 2017
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.
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