BHRF1 Enhances EBV Mediated Nasopharyngeal Carcinoma Tumorigenesis through Modulating Mitophagy Associated with Mitochondrial Membrane Permeabilization Transition

Cells

DavidEthan Spezia-Lindner¹  Yidong Bai¹  Ting Liang²  Zhiying Jiang²  Ye Tian³  Haifeng Wang³  Shujie Song⁴  Chang Xu⁵ 

[1] Department of Cell Systems and Anatomy, University of Texas Health San Antonio, San Antonio, TX 78258, USA;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;School of Medicine, Northwest University school of Medicine, Xi’an 710069, Shaanxi, China;School of Public Health, Xi’an Jiaotong University, Xi’an, 710048, Shaanxi, China;The Affiliated Hospital of Wenzhou Medical University, Wenzhou 325035, Zhejiang, China;

关键词: NPC;    EBV;    BHRF1;    mitochondria;    mitochondrial membrane permeabilization transition (MMPT);    mitophagy;   

DOI  :  10.3390/cells9051158

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown