title: Human SMG-1 is involved in gemcitabine-induced primary microRNA-155/BIC up-regulation in human pancreatic cancer PANC-1 cells.
abstract: OBJECTIVE
  Human primary microRNA-155/B-cell integration cluster (BIC) transcript is the precursor of microRNA-155. The overexpression of them has been widely observed in the progression of various types of tumors. Our objective was to investigate the effect of anticancer agents on the expression of BIC and possible signal pathways that involved in.
  
  
  METHODS
  Quantitative real-time reverse transcriptase polymerase chain reaction was used to measure the expression of BIC. Chemical inhibitors against c-Jun N-terminal kinase 1, mitogen-activated protein kinase/extracellular signal-regulated kinase kinase 1/2, protein kinase C, checkpoint kinase 1, and phosphatidylinositol 3 kinase (PI3K) were used for the evaluation of involved signal pathways. RNA interference was used to knock down the expression of ataxia-telangiectasia mutated, ataxia-telangiectasia and Rad3 related, and suppressor of morphogenesis in genitalia-1 (SMG-1), and Western blot was carried out to evaluate the knockdown effect.
  
  
  RESULTS
  B-cell integration cluster expression was induced by a representative anti-pancreatic cancer drug, gemcitabine, in human pancreatic cancer PANC-1 cells. The mitogen-activated protein kinase/extracellular signal-regulated kinase kinase 1/2 and c-Jun N-terminal kinase inhibitors, but not the checkpoint kinase 1 and protein kinase C inhibitors, suppressed the up-regulation of BIC. B-cell integration cluster up-regulation was also significantly inhibited by the PI3K inhibitor wortmannin. RNA interference studies showed that wortmannin-sensitive SMG-1 but not ataxia-telangiectasia mutated or ataxia-telangiectasia and Rad3 related was involved in the up-regulation.
  
  
  CONCLUSIONS
  Our results show that multiple pathways can be involved in the up-regulation of BIC. Furthermore, we demonstrate for the first time that PI3K SMG-1 is required for gemcitabine-induced up-regulation of BIC transcript.
authors.affiliation: Department of Medical Oncology, Kanazawa Medical University, Uchinada, Ishikawa, Japan.
authors.forename: Qi-sheng
authors.initials: QS
authors.lastname: Xia
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Ishigaki
authors.forename: Xia
authors.initials: X
authors.lastname: Zhao
authors.forename: Takeo
authors.initials: T
authors.lastname: Shimasaki
authors.forename: Hideo
authors.initials: H
authors.lastname: Nakajima
authors.forename: Hideaki
authors.initials: H
authors.lastname: Nakagawa
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Takegami
authors.forename: Zhi-hua
authors.initials: ZH
authors.lastname: Chen
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Motoo
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins / Q000502:physiology; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000502:physiology; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000502:physiology; D035683:MicroRNAs / Q000235:genetics*; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000502:physiology; D025521:Tumor Suppressor Proteins / Q000502:physiology; D015854:Up-Regulation; D000077191:Wortmannin; D000093542:Gemcitabine
chemical_list: D000730:Androstadienes; D000964:Antimetabolites, Antineoplastic; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D003841:Deoxycytidine; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D035683:MicroRNAs; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D025521:Tumor Suppressor Proteins; D000077191:Wortmannin; D000093542:Gemcitabine; C524942:MIRN155 microRNA, human; C576324:ATM protein, human; C576597:ATR protein, human; C514704:SMG1 protein, human