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Epstein‐Barr virus nuclear antigen 1 (EBNA1) protein induction of epithelial‐mesenchymal transition in nasopharyngeal carcinoma cells
Author(s) -
Wang Lu,
Tian WenDong,
Xu Xia,
Nie Biao,
Lu Juan,
Liu Xiong,
Zhang Bao,
Dong Qi,
Sunwoo John B.,
Li Gang,
Li XiangPing
Publication year - 2013
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.28418
Subject(s) - nasopharyngeal carcinoma , epithelial–mesenchymal transition , cancer research , biology , zinc finger , microrna , epstein–barr virus , cancer , virus , metastasis , virology , medicine , gene , transcription factor , genetics , radiation therapy
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 .