Lv Mengwen, Shi Duo, Zhao Xia, Zhang Yan, Liu Wen, Liu Shuzhen
Department of Blood Transfusion, The Affiliated Hospital of Qingdao University, No. 1677 Wutaishan Road, Qingdao, 266555, China.
Department of Pathogenic Biology, School of Basic Medicine, Qingdao University, Qingdao, 266071, China.
Virus Genes. 2025 Jul 15. doi: 10.1007/s11262-025-02178-8.
The key carcinogenic factor for nasopharyngeal cancer (NPC) is infection with the Epstein-Barr virus (EBV), significantly contributing to its occurrence and development. Insulin-like growth factor binding protein 2 (IGFBP2), known for its aberrant expression in various cancers, plays a pivotal role in oncogenic networks. Investigating IGFBP2's function and mechanism in EBV-associated NPC was the goal of the current study. The findings indicated that IGFBP2 expression was markedly higher in EBV-positive NPC cells compared to EBV-negative NPC cells, and EBV could up-regulate IGFBP2 expression by activating the TGF-β pathway through its encoded EBNA1. Furthermore, IGFBP2 influenced key carcinogenic processes, including proliferation, migration, epithelial-mesenchymal transition (EMT), and cell cycle progression in NPC cells. Notably, knockdown of IGFBP2 in the EBV-infected epithelial cell line C666-1 led to a reduction in the expression of EBV-encoded latent and lytic phase gene proteins, as well as a decrease in the copy number of the EBV genome. These results point to a reciprocal regulation link between EBV and IGFBP2, opening up a promising avenue for future clinical treatment and experimental research.
鼻咽癌（NPC）的关键致癌因素是感染爱泼斯坦-巴尔病毒（EBV），EBV对鼻咽癌的发生和发展有显著影响。胰岛素样生长因子结合蛋白2（IGFBP2）因在多种癌症中异常表达而闻名，在致癌网络中起关键作用。本研究的目的是探究IGFBP2在EBV相关鼻咽癌中的功能及机制。研究结果表明，与EBV阴性的NPC细胞相比，EBV阳性的NPC细胞中IGFBP2表达明显更高，且EBV可通过其编码的EBNA1激活TGF-β途径上调IGFBP2表达。此外，IGFBP2影响NPC细胞的关键致癌过程，包括增殖、迁移、上皮-间质转化（EMT）和细胞周期进程。值得注意的是，在EBV感染的上皮细胞系C666-1中敲低IGFBP2会导致EBV编码的潜伏和裂解期基因蛋白表达减少，以及EBV基因组拷贝数降低。这些结果表明EBV与IGFBP2之间存在相互调控关系，为未来的临床治疗和实验研究开辟了一条有前景的途径。
