Lawrence W Chamley

Placenta-derived trophoblast extracellular vesicles contain unique miRNAs that inhibit ovarian cancer cell growth

Abstract Previous reports have indicated that placental trophoblast extracellular vesicles (EVs) possess unique properties that enable them significantly to inhibit the proliferation of ovarian cancer cells in vitro and slow ovarian tumour growth in an in vivo model, while EVs derived from monocytes did not. However, the mechanisms underlying the inhibitory effects of trophoblast EVs remain unclear. In this study, we characterized the microRNAs (miRNAs) uniquely present in placental trophoblast EVs but absent from THP-1 monocyte-derived EVs. Through bioinformatic analysis, we elucidated the potential involvement of these unique miRNAs in the negative regulation of proliferation pathways implicated in ovarian cancer. Functional assays demonstrated that placental trophoblast EVs inhibited ovarian cancer cell proliferation, and this effect was reversed upon blocking EV uptake, indicating the transfer of the contents of the EVs as a crucial mechanism modulating cancer cell viability. Using miRNA mimics, we also demonstrated that specific miRNAs from placental trophoblast EVs exhibited inhibitory effects on ovarian cancer cell proliferation, highlighting the potential of placental trophoblast EVs as therapeutic agents. These findings not only shed light on the molecular mechanisms underlying the therapeutic efficacy of placental trophoblast EVs but also provide valuable insights into the potential development of miRNA-based therapies for ovarian cancer, including the use of trophoblast EVs as a therapeutic for ovarian cancer.