title: Epstein-Barr virus nuclear antigen 1 (EBNA1) protein induction of epithelial-mesenchymal transition in nasopharyngeal carcinoma cells.
abstract: BACKGROUND
  The Epstein-Barr virus (EBV)-encoded EB nuclear antigen 1 (EBNA1) protein is required for maintenance and transmission of the viral episome in EBV-infected cells. The objective of this study was to investigate the role of EBNA1 protein in nasopharyngeal carcinoma (NPC).
  
  
  METHODS
  Tissue samples from 48 patients with NPC and 12 patients with chronic nasopharyngitis were subjected to immunohistochemical analysis of EBNA1 expression. EBNA1 combinational DNA was used to overexpress EBNA1 protein in NPC cell lines to assess tumor cell epithelial-mesenchymal transition (EMT), colony formation, migration and invasion, and gene expression.
  
  
  RESULTS
  EBNA1 protein was highly expressed in NPC tissue specimens, and its expression was associated with NPC lymph node metastasis. EBNA1 expression affected NPC cell morphology and the expression of EMT markers in vitro. Furthermore, overexpression of EBNA1 inhibited the expression of microRNA 200a (miR-200a) and miR-200b and, in turn, up-regulated expression of their target genes, zinc finger E-box binding homeobox 1 ( ZEB1) and ZEB2, which are well known mediators of EMT. In addition, EBNA1-regulated miR-200a and miR-200b expression was mediated by transforming growth factor-β1.
  
  
  CONCLUSIONS
  The current findings provided novel insight into the vital role of EBNA1 in manipulating a molecular switch of EMT in EBV-positive NPC cells.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Wang
authors.forename: Wen-Dong
authors.initials: WD
authors.lastname: Tian
authors.forename: Xia
authors.initials: X
authors.lastname: Xu
authors.forename: Biao
authors.initials: B
authors.lastname: Nie
authors.forename: Juan
authors.initials: J
authors.lastname: Lu
authors.forename: Xiong
authors.initials: X
authors.lastname: Liu
authors.forename: Bao
authors.initials: B
authors.lastname: Zhang
authors.forename: Qi
authors.initials: Q
authors.lastname: Dong
authors.forename: John B
authors.initials: JB
authors.lastname: Sunwoo
authors.forename: Gang
authors.initials: G
authors.lastname: Li
authors.forename: Xiang-Ping
authors.initials: XP
authors.lastname: Li
mesh_terms: D002277:Carcinoma; D045744:Cell Line, Tumor; D002465:Cell Movement; D058750:Epithelial-Mesenchymal Transition; D019309:Epstein-Barr Virus Nuclear Antigens / Q000502:physiology*; D018398:Homeodomain Proteins / Q000502:physiology; D006801:Humans; D035683:MicroRNAs / Q000502:physiology; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000473:pathology*; D009361:Neoplasm Invasiveness; D015398:Signal Transduction; D014157:Transcription Factors / Q000502:physiology; D053773:Transforming Growth Factor beta1 / Q000502:physiology; D000071799:Zinc Finger E-box-Binding Homeobox 1
chemical_list: D019309:Epstein-Barr Virus Nuclear Antigens; D018398:Homeodomain Proteins; C533896:MIRN200 microRNA, human; D035683:MicroRNAs; D014157:Transcription Factors; D053773:Transforming Growth Factor beta1; C486307:ZEB1 protein, human; D000071799:Zinc Finger E-box-Binding Homeobox 1; C417029:EBV-encoded nuclear antigen 1
keywords: Epstein-Barr virus; epithelial-mesenchymal transition; metastasis; microRNA; nasopharyngeal carcinoma