Epstein-Barr virus protein can upregulate cyclo-oxygenase-2 expression through association with the suppressor of metastasis Nm23-H1
Authors: Subhash C Verma
Ke Lan
Masanao Murakami
Erle S Robertson
Rajeev Kaul
Tathagata Choudhuri
Journal: Journal of virology (2006)
Discipline: MICROBIOLOGY
Keywords: Epstein-Barr virus; EBNA3C; Nm23-H1; COX-2; cancer
Affiliations: Department of Microbiology, University of Pennsylvania School of Medicine, 201E Johnson Pavilion, 3610 Hamilton Walk, Philadelphia, PA 19104, USA., Department of Microbiology, University of Pennsylvania School of Medicine, and Tumor Virology Program, Abramson Comprehensive Cancer Center, Philadelphia, Pennsylvania 19104

Abstract:  Previous studies have demonstrated the interaction between the Epstein-Barr virus (EBV) nuclear antigen 3C (EBNA3C) and the metastatic suppressor Nm23-H1 both in vitro and in vivo (C. Subramanian, M. A. Cotter II, and E. S. Robertson, Nat. Med. 7:350-355, 2001). EBNA3C can reverse the ability of Nm23-H1 to suppress migration of Burkitt's lymphoma and breast carcinoma cell lines in vitro. EBNA3C contributes to EBV-associated human cancers by regulating transcription of a number of cellular and viral promoters and by targeting and altering the transcription activities of the metastasis suppressor Nm23-H1. Cyclo-oxygenase-2 (COX-2), an inducible enzyme important in inflammation, is overexpressed in a variety of cancers and can influence cell migration. In this report we show that Nm23-H1 and EBNA3C can modulate expression of COX-2 in the context of EBV infection and transformation. The levels of COX-2 were consistently higher in EBV-positive cells than in EBV-negative cells. Additionally, we show that Nm23-H1 can upregulate the COX-2 promoter element in luciferase reporter assays, whereas EBNA3C alone did not affect the level of response but clearly contributed to an additive increase when coexpressed with Nm23-H1. The downstream effect of COX-2 expression was also evaluated and showed that prostaglandin E(2) levels increased with Nm23-H1 and that there was some level of cooperativity in the presence of EBNA3C. The majority of this response was mediated through the cyclic AMP response element and NF-kappaB sites. These studies suggest a potential role for COX-2 in EBV-associated human cancers. 

Retracted: No

PubPeer comments:
 Figure 6B. * Red boxes: Lanes 2 and 5 appear to look unexpectedly similar. Note the little dot at the top of the lane, a scratch running just under the  Shift band, and a slanted faint band two thirds of the way down. ![file] , 
 Figure 2C. Much more similar than you would expect. https: imgur.com A8uhiLg , 
 Figure 6B. Much more similar than you would expect. https: imgur.com pYMpQd5 , 
 Last author appears to be on this journalu2019s editorial board: https: jvi.asm.org content board-editors , 
 Correction, July 2021, found here: https: journals.asm.org doi 10.1128 JVI.00744-21  * Page 1325, Fig. 2C: In the EBNA3C blot, the last band of the left subpanel and first band of the right subpanel are the same band obtained in the same experiment. This band is presented as data from a single experiment in the two adjacent subpanels for better visualization and simplicity. * Page 1327, Fig. 6B: Due to an error in figure assembly, the second lane is an inadvertent duplicate of the fifth lane. We have replaced the image using the correct original data. The lane between the currently labeled lane 4 and lane 5 was intentionally left blank. Figure 6B should appear as shown below. , 
 An additional finding for Figure 2C, in the a-EBNA2C panels, marked by me with orange boxes. ![file] Also, this paper appears to have a double PubPeer entry, found at: https: pubpeer.com publications 09597002AD4C31228FA0DF92825BA2 ,