School of Public Health, Xi'an Jiaotong University, Xi'an, 710048, Shaanxi, China.
Key Laboratory of Laboratory Medicine, Ministry of Education, Zhejiang Provincial Key Laboratory of Medical Genetics, College of Laboratory Medicine and Life sciences, Wenzhou Medical University, Wenzhou 325035, Zhejiang, China.
Cells. 2020 May 7;9(5):1158. doi: 10.3390/cells9051158.
Epstein-Barr virus (EBV) is a major contributor to nasopharyngeal carcinoma (NPC) tumorigenesis. Mitochondria have been shown to be a target for tumor viral invasion, and to mediate viral tumorigenesis. In this study, we detected that mitochondrial morphological changes in tumor tissues of NPC patients infected with EBV were accompanied by an elevated expression of BHRF1, an EBV encoded protein homologue to Bcl-2. High expression of BHRF1 in human NPC cell lines enhanced tumorigenesis and metastasis features. With BHRF1 localized to mitochondria, its expression induced cyclophlin D dependent mitochondrial membrane permeabilization transition (MMPT). The MMPT further modulated mitochondrial function, increased ROS production and activated mitophagy, leading to enhanced tumorigenesis. Altogether, our results indicated that EBV-encoded BHRF1 plays an important role in NPC tumorigenesis through regulating cyclophlin D dependent MMPT.
EBV 病毒（EBV）是鼻咽癌（NPC）肿瘤发生的主要因素。已经表明线粒体是肿瘤病毒入侵的靶点，并介导病毒的肿瘤发生。在这项研究中，我们检测到 EBV 感染 NPC 患者肿瘤组织中线粒体形态发生变化，同时 BHRF1 的表达升高，BHRF1 是 EBV 编码的与 Bcl-2 同源的蛋白。人 NPC 细胞系中 BHRF1 的高表达增强了致瘤性和转移特征。BHRF1 定位于线粒体，其表达诱导细胞色素 P450 依赖性线粒体膜通透性过渡（MMPT）。MMPT 进一步调节线粒体功能，增加 ROS 产生并激活线粒体自噬，从而增强致瘤性。总之，我们的结果表明，EBV 编码的 BHRF1 通过调节细胞色素 P450 依赖性 MMPT 在 NPC 肿瘤发生中起重要作用。
