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Functional interaction of Ugene and EBV infection mediates tumorigenic effects

Oncogene volume 30, pages 2921–2932 (2011)Cite this article

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Abstract

Epstein–Barr virus (EBV) infection is associated with many human neoplasms, in which EBV-derived latent membrane protein-1 (LMP1) appears to be critical, but its exact oncogenic mechanism remains to be defined. To this end, our initial microarray analyses identified a LMP1-inducible gene, Ugene, originally characterized as a binding partner for uracil DNA glycosylase 2, which is highly expressed in malignant colon cancer. In this report, it was found that Ugene, designated herein as LMP1-induced protein (LMPIP), was induced, in a time-dependent manner, in EBV-infected peripheral blood mononuclear cells and LMP1-transfected 293 cells. Functionally, when compared with mock-transfected cells, overexpression of LMPIP in nasopharyngeal carcinoma (NPC) cell lines resulted in a decrease in reactive oxygen species production and maintained mitochondria membrane potential (Δψ) loss induced by H2O2. The NPC cells transfected with LMPIP also showed a decrease in G1 population and an increase in the cell population in sub-G1 and multiploid phase, concomitant with increased levels of cell cycle activators, including cyclin D1 and CDK4. In contrast, silencing of LMPIP expression in the NPC tumor cell lines with short hairpin RNA interference revealed significantly decreased cell population at G1/S phase, while the number of cells in multiploid phase increased. Significantly, NPC cells with LMPIP knock-down also showed a decrease in tumorigenic and transforming activity induced by ectopic LMP1 expression, as determined by analyses of soft agar foci and tumor size in nude mice. Further, elevated LMPIP expression was also noted in cytoplasm and nuclei in EBV-infected NPC tumor cell mass and non-EBV-infected tumor cell lines. These results suggested that LMPIP may have an important mediator role in EBV-mediated neoplasm and may serve as a new target for therapy of tumors induced by EBV infection.

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Acknowledgements

We thank Dr SK Huang for critically reviewing this paper. This work was supported in part by Research Grants NSC-97-2311-B-037-002-MY3, NSC-97-2314-B-037-015 and NSC-98-2320-B- 037-026-MY3 from the National Science Council, Taiwan.

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Authors and Affiliations

  1. Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

    L-T Wang, C-S Lin, K-Y Liu & S-H Hsu

  2. Department of Pathology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

    C-Y Chai

  3. Institute of Cancer Research, National Health Research Institutes, Zhunan, Taiwan

    J-Y Chen

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  1. L-T Wang
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Correspondence to S-H Hsu.

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Wang, LT., Lin, CS., Chai, CY. et al. Functional interaction of Ugene and EBV infection mediates tumorigenic effects. Oncogene 30, 2921–2932 (2011). https://doi.org/10.1038/onc.2011.16

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