人类巨细胞病毒（HCMV）感染被认为与上皮性卵巢癌（OC）有关。高级别浆液性卵巢癌（HGSOC）中观察到多倍体巨细胞癌细胞（PGCCs），它们具有类似癌干细胞的特性，并产生表达上皮间质转化（EMT）标记的后代细胞。EZH2发挥潜在的致癌作用，与OC中的高增殖指数和肿瘤分级相关。在这里，我们提出了HCMV作为一种重新编程载体引发人卵巢上皮细胞（OECs）转化从而产生“CMV转化的卵巢细胞”（CTO）的实验证据。感染两种高风险的临床菌株，即HCMV-DB和BL，在感染的OECs中引发了明显的细胞和分子机制。使用EZH2抑制剂可以减缓EZH2上调和细胞增殖。HGSOC活检表现出EZH2表达升高，与上述标记物和HCMV之间存在明显的正相关。我们从HGSOC活检中分离出3种HCMV临床菌株，这些菌株转化OECs，产生显示增殖潜力以及EZH2上调和PGCCs生成的CTO细胞；这些特征在EZH2抑制剂作用下减少。高风险的HCMV菌株转化OECs，证实了HCMV诱导的上皮性卵巢癌模型，突显了EZH2的肿瘤性质。我们的研究结果对卵巢肿瘤的病理生理学可能非常相关，从而提名了新的靶向治疗方法。©2023年。作者

Human cytomegalovirus (HCMV) infection has been implicated in epithelial ovarian cancer (OC). Polyploidy giant cancer cells (PGCCs) have been observed in high-grade serous ovarian carcinoma (HGSOC); they possess cancer stem cell-like characteristics and give rise to progeny cells expressing epithelial-mesenchymal transition (EMT) markers. EZH2 plays a potential oncogenic role, correlating with high proliferative index and tumor grade in OC. Herein, we present the experimental evidence for HCMV as a reprogramming vector that elicited human ovarian epithelial cells (OECs) transformation leading to the generation of "CMV-transformed Ovarian cells" (CTO). The infection with the two high-risk clinical strains, namely HCMV-DB and BL provoked a distinct cellular and molecular mechanisms in infected OECs. EZH2 upregulation and cellular proliferation were curtailed by using EZH2 inhibitors. The HGSOC biopsies were characterized by an elevated EZH2 expression, possessing a strong positive correlation between the aforementioned marker and HCMV. From HGSOC biopsies, we isolated three HCMV clinical strains that transformed OECs generating CTO cells which displayed proliferative potentials in addition to EZH2 upregulation and PGCCs generation; these features were reduced upon EZH2 inhibition. High-risk HCMV strains transformed OECs confirming an HCMV-induced epithelial ovarian cancer model and highlighting EZH2 tumorigenic properties. Our findings might be highly relevant in the pathophysiology of ovarian tumors thereby nominating new targeted therapeutics.© 2023. The Author(s).