Epstein-Barr virus nuclear antigen 1 (EBNA1) protein induction of epithelial-mesenchymal transition in nasopharyngeal carcinoma cells
Lu Wang, Wen-Dong Tian, Xia Xu, Biao Nie, Juan Lu, Xiong Liu, Bao Zhang, Qi Dong, John B Sunwoo, Gang Li, Xiang-Ping Li, Lu Wang, Wen-Dong Tian, Xia Xu, Biao Nie, Juan Lu, Xiong Liu, Bao Zhang, Qi Dong, John B Sunwoo, Gang Li, Xiang-Ping Li
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.
Keywords: Epstein-Barr virus; epithelial-mesenchymal transition; metastasis; microRNA; nasopharyngeal carcinoma.
© 2013 American Cancer Society.
Source: PubMed