Introduction:It is now well-recognised that phagocytosis of placental EVs impacts the function of the recipient cells by releasing of their cargos, including proteins and miRNAs. We have previously reported that phagocytosis of placental EVs inhibited the growth of SKOV-3 ovarian cancer cells. However, the mechanism underlying this inhibitory effect is unknown. recent miRNA sequencing data showed that some miRNAs contained in placental EVs including miRNA-519a-5p and miRNA-143-3p, are associated with the promotion of ovarian cancer cell death. In this study, we further investigated whether there is a change in these miRNAs in SKOV-3 after exposure to placental EVs.
Methods:Placental EVs were collected from first trimester placentae (n=4) and SKOV-3 cells were treated with placental micro- or nano-EVs for 24 hours in triplicate. The levels of miRNA-519a-5p, miRNA-512-3p, and miRNA-143-3p were measured in SKOV-3 cells. In addition, mRNA levels of G3BP1 and BCL2L2 which are target genes of miRNA-519a-5p were also measured.
Results:The levels of miRNA-519a-5p, miRNA-512-3p, and miRNA-143-3p were significantly increased, and the mRNA levels of G3BP1 and BCL2L2 were decreased in SKOV-3 after exposure to placental EVs. Transfection of SKOV-3 cells with a mimic of miRNA-519a-5p or miRNA-143-3p significantly reduced cell viability. However, the levels of miRNA-519a-5p returned to baseline in the daughter cells after passaging the SKOV-3 cells. When the daughter cells were exposed to fresh placental EVs, the levels of miRNA-519a-5p significantly increased as in the parental cells.
Discussion:our data demonstrated that phagocytosis of placental EVs contributed to the death of ovarian cancer cells, possibly through increasing the levels of death associated.