title: Epstein-Barr virus-encoded LMP1 increases miR-155 expression, which promotes radioresistance of nasopharyngeal carcinoma via suppressing UBQLN1.
abstract: OBJECTIVE
  Epstein-Barr virus (EBV)-encoded latent membrane protein (LMP1) can drive aberrant expression of miR-155 in nasopharyngeal carcinoma (NPC). In this study, we investigated the regulation of miR-155 expression over UBQLN1 and studied their effects on radio-sensitivity of NPC.
  
  
  METHODS
  MiR-155, LMP1 and ubiquilin-1 expression were measured in 40 cases of NPC cases. The regulative role of miR-155 over UBQLN1 was investigated using a dual luciferase assay, qRT-PCR and Western blot analysis. The effect of miR-155-UBQLN1 axis on radio-sensitivity was explored using loss-and-gain study. The activation of PI3K/Akt pathway and the expression change of some important genes regulating cell cycle, cell proliferation and epithelial-to-mesenchymal transition (EMT) were measured.
  
  
  RESULTS
  MiR-155 was significantly increased in radio-resistant NPC tissues and was negatively correlated to ubiqulin-1 expression. LMP1 overexpression led to significantly higher miR-155 expression. MiR-155 had two binding sites with 3'UTR of UBQLN1 and could decrease it expression. MiR-155 overexpression increased survival fraction of CNE-2 cells after exposure to 6 Gy and decreased cell apoptosis. It also partly abrogated the inhibiting effect of UBQLN1. Through decreasing ubiqulin-1, miR-155 changed the cell cycle to a more radio-resistant model. The miR-155-UBQLN1 axis affected the activation of PI3K/Akt pathway in NPC cells and changed the expression of some important genes regulating the cell cycle, cell proliferation and EMT.
  
  
  CONCLUSIONS
  This study found that aberrant miR-155 expression driven by LMP1 can modulate radio-sensitivity of the NPC cell at least partly through targeting UBQLN1.
authors.affiliation: Department of Oncology, Daqing Oilfield General Hospital, Daqing, China. chunmeihu80@tom.com.
authors.forename: F
authors.initials: F
authors.lastname: Yang
authors.forename: Q
authors.initials: Q
authors.lastname: Liu
authors.forename: C-M
authors.initials: CM
authors.lastname: Hu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D017209:Apoptosis / Q000528:radiation effects; D000071183:Autophagy-Related Proteins; D002277:Carcinoma; D002352:Carrier Proteins / Q000096:biosynthesis*; D002453:Cell Cycle / Q000528:radiation effects; D018797:Cell Cycle Proteins / Q000096:biosynthesis*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000528:radiation effects; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis*; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism* / Q000532:radiotherapy*; D011836:Radiation Tolerance / Q000502:physiology*; D014763:Viral Matrix Proteins / Q000096:biosynthesis*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; C037662:EBV-associated membrane antigen, Epstein-Barr virus; C524942:MIRN155 microRNA, human; D035683:MicroRNAs; C107792:UBQLN1 protein, human; D014763:Viral Matrix Proteins