title: Targeting EBV-LMP1 DNAzyme enhances radiosensitivity of nasopharyngeal carcinoma cells by inhibiting telomerase activity.
abstract: The latent membrane protein 1 (LMP1), which is encoded by the Epstein-Barr virus (EBV), has been suggested to be one of the major oncogenic factors in nasopharyngeal carcinoma (NPC). In previous studies, we experimentally demonstrated that downregulation of LMP1 expression by targeting EBV-LMP1 DNAzyme (Dz1) could increase the radiosensitivity of NPC. However, how Dz1 contributes to the radiosensitivity in NPC is still not clear. In the present study, we confirmed that Dz1 decreases LMP1 expression and downregulates the expression of the catalytic subunit of telomerase (hTERT), both at the protein and mRNA levels (P<0.01), and therefore, consequently inhibits telomerase activity (P<0.05) in LMP1-positive NPC cells. We also observed that LMP1 mediated Akt phosphorylation is involved in the regulation of hTERT expression and phosphorylation. After LMP1 and hTERT expression was silenced by Dz1 and hTERT-targeted siRNA, respectively, the radiosensitivity increased in CNE1-LMP1 cells (P<0.05). The inhibition was more significant after Dz1 treatment was combined with siRNA (P<0.01). We concluded that hTERT expression and phosphorylation could be regulated by LMP1 through the Akt pathway, and Dz1 enhances radiosensitivity of LMP1-positive NPC cells by inhibiting telomerase activity.
authors.affiliation: Cancer Research Institute; Xiangya School of Medicine; Central South University; Changsha, PR China; Center for Molecular Medicine; Xiangya Hospital; Central South University; Changsha, PR China.
authors.forename: Lifang
authors.initials: L
authors.lastname: Yang
authors.affiliation: Cancer Research Institute; Xiangya School of Medicine; Central South University; Changsha, PR China.
authors.forename: Zhijie
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Cancer Research Institute; Xiangya School of Medicine; Central South University; Changsha, PR China.
authors.forename: Liyu
authors.initials: L
authors.lastname: Liu
authors.affiliation: Cancer Research Institute; Xiangya School of Medicine; Central South University; Changsha, PR China.
authors.forename: Xiangjian
authors.initials: X
authors.lastname: Luo
authors.affiliation: Cancer Research Institute; Xiangya School of Medicine; Central South University; Changsha, PR China.
authors.forename: Jingchen
authors.initials: J
authors.lastname: Lu
authors.affiliation: Center for Molecular Medicine; Xiangya Hospital; Central South University; Changsha, PR China.
authors.forename: Lunquan
authors.initials: L
authors.lastname: Sun
authors.affiliation: Cancer Research Institute; Xiangya School of Medicine; Central South University; Changsha, PR China.
authors.forename: Ya
authors.initials: Y
authors.lastname: Cao
mesh_terms: D002277:Carcinoma; D045744:Cell Line, Tumor / Q000528:radiation effects; D021881:DNA, Catalytic / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000201:enzymology / Q000473:pathology*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D011836:Radiation Tolerance; D015398:Signal Transduction; D019098:Telomerase / Q000235:genetics / Q000378:metabolism*; D014763:Viral Matrix Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D021881:DNA, Catalytic; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D034741:RNA, Small Interfering; D014763:Viral Matrix Proteins; D051057:Proto-Oncogene Proteins c-akt; D019098:Telomerase
keywords: Akt; DNAzyme; LMP1; NPC; hTERT; radiosensitivity; telomerase