Epstein-Barr virus-encoded LMP1 increases miR-155 expression, which promotes radioresistance of nasopharyngeal carcinoma via suppressing UBQLN1.

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. MATERIALS AND 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.