Department of Emergency, Jinan Children's Hospital, Jinan, 250022, People's Republic of China.
Department of Hematology, Binzhou People's Hospital, Binzhou, 256600, People's Republic of China.
Arch Virol. 2023 May 3;168(5):150. doi: 10.1007/s00705-023-05774-x.
Epstein-Barr virus immediate-early protein Zta plays an active role in altering cellular gene expression, which may be fundamentally linked to the viral life cycle, cell cycle, cell growth, and differentiation. HER2 is associated with a wide variety of human cancers, and its knockdown significantly reverses the malignant features of HER2-positive cancers. The aim of this study was to investigate the potential role of Zta in regulating HER2 expression and phenotype changes of MDA-MB-453 cells. Our results indicate that ectopic expression of Zta resulted in downregulation of the HER2 protein in cancer cells (MDA-MB-453, SKBR-3, BT474, and SKOV-3). The Zta protein significantly decreased HER2 mRNA and protein expression in MDA-MB-453 cells in a dose-dependent manner. Mechanistically, Zta recognized and targeted the promoter of HER2 gene, reducing the transcriptional activity of the HER2 gene. Zta induced G0/G1 arrest of MDA-MB-453 cells, inhibiting their proliferation and migration activity. These data suggest that Zta may act as a transforming suppressor of the HER2 gene.
EB 病毒早期蛋白 Zta 在改变细胞基因表达方面发挥着积极作用，这可能与病毒生命周期、细胞周期、细胞生长和分化有根本联系。HER2 与多种人类癌症相关，其敲低可显著逆转 HER2 阳性癌症的恶性特征。本研究旨在探讨 Zta 在调节 MDA-MB-453 细胞中 HER2 表达和表型变化中的潜在作用。我们的结果表明，Zta 的异位表达导致癌细胞（MDA-MB-453、SKBR-3、BT474 和 SKOV-3）中 HER2 蛋白下调。Zta 蛋白以剂量依赖性方式显著降低 MDA-MB-453 细胞中 HER2 mRNA 和蛋白的表达。从机制上讲，Zta 识别并靶向 HER2 基因的启动子，降低了 HER2 基因的转录活性。Zta 诱导 MDA-MB-453 细胞的 G0/G1 期阻滞，抑制其增殖和迁移活性。这些数据表明，Zta 可能作为 HER2 基因的转化抑制因子发挥作用。
