title: Reversal effect of GnT-V on the radioresistance of human nasopharyngeal carcinoma cells by alteration β1, 6-GlcNAc branched N-glycans.
abstract: Radiotherapy is the primary treatment for human nasopharyngeal carcinoma (NPC), yet radioresistance remains a major obstacle to successful treatment in many cases. N-acetylglucosaminyltransferase V (GnT-V), which synthesizes β1, 6-GlcNAc branched N-glycans, is closely related to the radiosensitivity of NPC cells. However, a better understanding of the functional role of GnT-V in NPC radioresistance and the related mechanisms is urgently needed. In the present study, a radioresistant NPC cell line, CNE-2R, was established by repeated γ-irradiation. We found that GnT-V levels, as well as β1, 6-GlcNAc branched N-glycans were significantly increased in the CNE-2R cells as compared with that in the parental cells. Meanwhile, knockdown of GnT-V in the CNE-2R cells enhanced cell radiosensitivity and inhibited the formation of β1, 6-branched N-glycans. In addition, the regulated expression of GnT-V in the CNE-2R cells converted the heterogeneous N-glycosylated forms of CD147. Furthermore, swainsonine, an inhibitor of N-glycan biosynthesis, was also able to reverse the radioresistance of the CNE-2R cells. Taken together, the present study revealed a novel mechanism of GnT-V as a regulator of radioresistance in NPC cells, which may be useful for fully understanding the biological role of N-glycans in NPC radioresistance.
authors.affiliation: Center for Evidence-based Medicine and Clinical Research, Taihe Hospital, Hubei University of Medicine 32 South Renmin Road, Shiyan 442000, Hubei, P. R. China ; Department of Clinical Oncology, Taihe Hospital, Hubei University of Medicine 32 South Renmin Road, Shiyan 442000, Hubei, P. R. China.
authors.forename: Jun-Bo
authors.initials: JB
authors.lastname: Wu
authors.affiliation: Department of Clinical Oncology, Taihe Hospital, Hubei University of Medicine 32 South Renmin Road, Shiyan 442000, Hubei, P. R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Shen
authors.affiliation: Department of Clinical Oncology, Taihe Hospital, Hubei University of Medicine 32 South Renmin Road, Shiyan 442000, Hubei, P. R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Qiu
authors.affiliation: Department of Clinical Oncology, Taihe Hospital, Hubei University of Medicine 32 South Renmin Road, Shiyan 442000, Hubei, P. R. China.
authors.forename: Qi-Wen
authors.initials: QW
authors.lastname: Duan
authors.affiliation: Department of Clinical Oncology, Taihe Hospital, Hubei University of Medicine 32 South Renmin Road, Shiyan 442000, Hubei, P. R. China.
authors.forename: Zhi-Guo
authors.initials: ZG
authors.lastname: Luo
authors.affiliation: Department of Pharmacology, Hubei University of Medicine 30 South Renmin Road, Shiyan 442000, Hubei, P. R. China.
authors.forename: Xiao-Xia
authors.initials: XX
authors.lastname: Dong
mesh_terms: D017209:Apoptosis / Q000528:radiation effects; D015153:Blotting, Western; D002277:Carcinoma; D045744:Cell Line, Tumor; D005434:Flow Cytometry; D006801:Humans; D017351:N-Acetylglucosaminyltransferases / Q000378:metabolism*; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism*; D011134:Polysaccharides / Q000378:metabolism*; D034741:RNA, Small Interfering; D011836:Radiation Tolerance / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
chemical_list: D011134:Polysaccharides; D034741:RNA, Small Interfering; C000601122:Mgat5 protein, human; D017351:N-Acetylglucosaminyltransferases
keywords: GnT-V; N-glycans; nasopharyngeal carcinoma; radioresistance