title: Functional interaction of Ugene and EBV infection mediates tumorigenic effects.
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 H(2)O(2). 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.
authors.affiliation: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: L-T
authors.initials: LT
authors.lastname: Wang
authors.forename: C-S
authors.initials: CS
authors.lastname: Lin
authors.forename: C-Y
authors.initials: CY
authors.lastname: Chai
authors.forename: K-Y
authors.initials: KY
authors.lastname: Liu
authors.forename: J-Y
authors.initials: JY
authors.lastname: Chen
authors.forename: S-H
authors.initials: SH
authors.lastname: Hsu
mesh_terms: D000818:Animals; D002144:Callithrix; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002472:Cell Transformation, Viral / Q000235:genetics*; D002478:Cells, Cultured; D004843:Epistasis, Genetic / Q000502:physiology*; D020031:Epstein-Barr Virus Infections / Q000150:complications* / Q000235:genetics / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000473:pathology; D008565:Membrane Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011817:Rabbits; D014018:Tissue Distribution; D014162:Transfection; D014183:Transplantation, Heterologous; D014763:Viral Matrix Proteins / Q000235:genetics
chemical_list: D002352:Carrier Proteins; C037662:EBV-associated membrane antigen, Epstein-Barr virus; C531184:FAM72A protein, human; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D014763:Viral Matrix Proteins