title: c-Jun NH2-terminal kinase activation is essential for up-regulation of LC3 during ceramide-induced autophagy in human nasopharyngeal carcinoma cells.
abstract: BACKGROUND
  Autophagy is a dynamic catabolic process characterized by the formation of double membrane vacuoles termed autophagosomes. LC3, a homologue of yeast Atg8, takes part in autophagosome formation, but the exact regulation mechanism of LC3 still needs to be elucidated.
  
  
  METHODS
  Ceramide-induced autophagy was determined by detecting LC3 expression with Western blotting and confocal microscopy in human nasopharyngeal carcinoma cell lines CNE2 and SUNE1. The activation of JNK pathway was assessed by Western blotting for phospho-specific forms of JNK and c-Jun. The JNK activity specific inhibitor, SP600125, and siRNA directed against JNK were used to block JNK/c-Jun pathway. ChIP and luciferase reporter analysis were applied to determine whether c-Jun was involved in the regulation of LC3 transcription.
  
  
  RESULTS
  Ceramide-treated cells exhibited the characteristics of autophagy and JNK pathway activation. Inhibition of JNK pathway could block the ceramide-induced autophagy and the up-regulation of LC3 expression. Transcription factor c-Jun was involved in LC3 transcription regulation in response to ceramide treatment.
  
  
  CONCLUSIONS
  Ceramide could induce autophagy in human nasopharyngeal carcinoma cells, and activation of JNK pathway was involved in ceramide-induced autophagy and LC3 expression.
authors.affiliation: State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-Sen University, Guangzhou 510060, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Sun
authors.forename: DanDan
authors.initials: D
authors.lastname: Li
authors.forename: Linlin
authors.initials: L
authors.lastname: Wang
authors.forename: LiangPing
authors.initials: L
authors.lastname: Xia
authors.forename: JianGuo
authors.initials: J
authors.lastname: Ma
authors.forename: Zhong
authors.initials: Z
authors.lastname: Guan
authors.forename: GongKan
authors.initials: G
authors.lastname: Feng
authors.forename: XiaoFeng
authors.initials: X
authors.lastname: Zhu
mesh_terms: D000873:Anthracenes / Q000494:pharmacology; D001343:Autophagy / Q000187:drug effects*; D002277:Carcinoma; D045744:Cell Line, Tumor; D002518:Ceramides / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000235:genetics* / Q000378:metabolism; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D034741:RNA, Small Interfering / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014158:Transcription, Genetic / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D000873:Anthracenes; D002518:Ceramides; C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; C432165:pyrazolanthrone; D048031:JNK Mitogen-Activated Protein Kinases