Sun Xinyi, Wan Jiayi, Zhang Yi, Shen Ye, Tang Yunhui, Yin Yongxiang, Chamley Lawrence W, Zhao Min, Chen Qi
Department of Obstetrics & Gynaecology, The University of Auckland, New Zealand.
Department of Pathology, Wuxi No 2 People's Hospital, Nanjing Medical University, China.
Placenta. 2025 Feb;160:20-28. doi: 10.1016/j.placenta.2024.12.028. Epub 2024 Dec 31.
Placental extracellular vesicles (EVs), lipid-enclosed particles released from the placenta, can facilitate intercellular communication and are classified as micro- or nano-EVs depending on size. Placental EVs contain molecules associated with cell proliferation and death. In this study, we investigated whether treating human ovarian tumour explants with placental EVs could induce ovarian tumour cell death.
Human ovarian tumours were collected. After directly treating human ovarian tumour explants with placental EVs, cellular necrosis was observed in ovarian tumour explants by HE stains. Cell death-associated miRNAs were measured.
Expression of apoptosis and senescence-associated proteins, including NF-κβ and γ H2AX, were significantly increased, while proliferation-associated proteins were significantly reduced in the explants after exposure to placental EVs. Furthermore, miRNA-519a-5p, miRNA-512-3p and miRNA-143-3p, which were reported to promote ovarian cancer cell apoptosis or inhibition of ovarian cancer cell growth, were significantly increased, and the target genes of miRNA-519a-5p and miRNA-512-3p were significantly reduced in the explants after exposure to placental EVs. Transfection of SK-OV-3 ovarian cancer cells with a mimic of miRNA-519a-5p or miRNA-143-3p reduced the viability of these cells.
Our study demonstrated that placental EVs could induce necrosis in ovarian tumour explants. Increased levels of apoptosis and senescence-associated proteins and miRNAs could contribute to this change in ovarian tumour cell phenotype after exposure to placental EVs.
胎盘细胞外囊泡（EVs）是胎盘释放的脂质包裹颗粒，可促进细胞间通讯，并根据大小分为微囊泡或纳米囊泡。胎盘细胞外囊泡含有与细胞增殖和死亡相关的分子。在本研究中，我们调查了用胎盘细胞外囊泡处理人卵巢肿瘤外植体是否能诱导卵巢肿瘤细胞死亡。
收集人卵巢肿瘤。在用胎盘细胞外囊泡直接处理人卵巢肿瘤外植体后，通过苏木精-伊红（HE）染色观察卵巢肿瘤外植体中的细胞坏死情况。检测与细胞死亡相关的微小RNA（miRNAs）。
暴露于胎盘细胞外囊泡后，外植体中凋亡和衰老相关蛋白（包括核因子κB（NF-κβ）和γH2AX）的表达显著增加，而增殖相关蛋白显著减少。此外，据报道可促进卵巢癌细胞凋亡或抑制卵巢癌细胞生长的miRNA-519a-5p、miRNA-512-3p和miRNA-143-3p显著增加，暴露于胎盘细胞外囊泡后的外植体中miRNA-519a-5p和miRNA-512-3p的靶基因显著减少。用miRNA-519a-5p或miRNA-143-3p模拟物转染SK-OV-3卵巢癌细胞可降低这些细胞的活力。
我们的研究表明，胎盘细胞外囊泡可诱导卵巢肿瘤外植体坏死。凋亡和衰老相关蛋白及miRNAs水平的升高可能导致暴露于胎盘细胞外囊泡后卵巢肿瘤细胞表型的这种变化。
