Epstein‐Barr virus nuclear antigen 1 (EBNA1) protein induction of epithelial‐mesenchymal transition in nasopharyngeal carcinoma cells

• Published in: Cancer Vol. 120; no. 3; pp. 363 - 372
• Main Authors: Wang, Lu, Tian, Wen‐Dong, Xu, Xia, Nie, Biao, Lu, Juan, Liu, Xiong, Zhang, Bao, Dong, Qi, Sunwoo, John B., Li, Gang, Li, Xiang‐Ping
• Format: Journal Article
• Language: English
• Published: Hoboken, NJ Wiley-Blackwell 01.02.2014
• Subjects: Biological and medical sciences; Carcinoma; Cell Line, Tumor; Cell migration; Cell Movement; Epithelial-Mesenchymal Transition; Epstein-Barr virus; Epstein-Barr Virus Nuclear Antigens - physiology; Homeodomain Proteins - physiology; Humans; Medical sciences; metastasis; microRNA; MicroRNAs - physiology; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms - pathology; Neoplasm Invasiveness; Otorhinolaryngology. Stomatology; Signal Transduction; Transcription Factors - physiology; Transforming Growth Factor beta1 - physiology; Tumors; Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology; Zinc Finger E-box-Binding Homeobox 1; RNA interference; Nasopharynx cancer; Epstein Barr virus; Nasopharynx carcinoma; Metastasis; Cell transformation; Cancerology; ENT disease; Pharynx disease; Epstein-Barr virus; epithelial-mesenchymal transition; Cell; Gammaherpesvirinae; nasopharyngeal carcinoma; Induction; Herpesviridae; Micro RNA; Malignant tumor; Protein; Infection; Virus; Gene silencing; Viral disease; microRNA; Epithelial mesenchymal transition; Cancer; metastasis
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/cncr.28418

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. Cancer 2014;120:363–372. © 2013 American Cancer Society. The role of Epstein‐Barr virus nuclear antigen 1 (EBNA1) in nasopharyngeal carcinoma is investigated with regard to EBNA1 protein induction of epithelial‐mesenchymal transition in nasopharyngeal carcinoma cells. The results demonstrate that EBNA1 promotes metastasis of human nasopharyngeal carcinoma through the TGFβ/miR‐200/ZEB pathway.