title: LMP1 promotes nasal NK/T-cell lymphoma cell function by eIF4E via NF-κB pathway.
abstract: Nasal natural killer T-cell lymphoma (NKTL) is a highly malignant tumor that is closely associated with Epstein-Barr virus (EBV) infection. Latent membrane protein 1 (LMP1) is encoded by EBV and plays an important role in EBV-induced cell transformation. Therefore, we assessed the function of LMP1 as a stimulant of NKTL progression and the underlying mechanism. A human EBV-positive NKTL cell line (SNK-6) was transfected with pcDNA3.1-LMP1, LV-LMP1 shRNA or LV-eukaryotic translation initiation factor 4E (eIF4E)-shRNA. Then, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was used to assess the proliferation of SNK-6 cells, and cell migration and invasion were analyzed by transwell chamber assay. Flow cytometry was used to analyze the cell cycle and apoptosis. The results showed LMP1 was highly expressed in SNK-6 cells compared with control groups. Following pretreatment with LMP1 shRNA, the proliferation of SNK-6 cells was inhibited and resulted in a G0/G1 phase arrest. A reduction in invasion and migration was also observed. LMP1 silencing promoted cell apoptosis. Further mechanistic analysis suggested that LMP1 overexpression induced the expression of eIF4E, while eIF4E-shRNA dramatically attenuated the increase in cell proliferation, invasion, migration and the inhibition of apoptosis triggered by LMP-1 upregulation. Moreover, the effect of LMP1 on eIF4E expression was mediated by the NF-κB pathway. Therefore, this finding may provide a potential target against NKTL.
authors.affiliation: Department of Pathology, Hainan Branch of PLA General Hospital, Sanya 572000, P.R. China.
authors.forename: Lu
authors.initials: L
authors.lastname: Sun
authors.affiliation: Department of Hematology, PLA General Hospital, Beijing 100853, P.R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Pathology, PLA General Hospital, Beijing 100853, P.R. China.
authors.forename: Huaiyin
authors.initials: H
authors.lastname: Shi
authors.affiliation: Department of Hematology, PLA General Hospital, Beijing 100853, P.R. China.
authors.forename: Chao
authors.initials: C
authors.lastname: Ma
authors.affiliation: Department of Pathology, PLA General Hospital, Beijing 100853, P.R. China.
authors.forename: Lixin
authors.initials: L
authors.lastname: Wei
mesh_terms: D017209:Apoptosis / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D020031:Epstein-Barr Virus Infections / Q000235:genetics* / Q000473:pathology / Q000821:virology; D039561:Eukaryotic Initiation Factor-4E / Q000096:biosynthesis / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D004854:Herpesvirus 4, Human / Q000472:pathogenicity; D006801:Humans; D016399:Lymphoma, T-Cell / Q000235:genetics* / Q000473:pathology / Q000821:virology; D055611:Natural Killer T-Cells / Q000473:pathology / Q000821:virology; D009361:Neoplasm Invasiveness / Q000235:genetics; D009669:Nose Neoplasms / Q000235:genetics* / Q000473:pathology / Q000821:virology; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D014763:Viral Matrix Proteins / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C037662:EBV-associated membrane antigen, Epstein-Barr virus; D039561:Eukaryotic Initiation Factor-4E; D034741:RNA, Small Interfering; D014763:Viral Matrix Proteins