title: MicroRNA-1246 expression associated with CCNG2-mediated chemoresistance and stemness in pancreatic cancer.
abstract: BACKGROUND
  Pancreatic cancer has a poor prognosis because of its high refractoriness to chemotherapy and tumour recurrence, and these properties have been attributed to cancer stem cells (CSCs). MicroRNA (miRNA) regulates various molecular mechanisms of cancer progression associated with CSCs. This study aimed to identify the candidate miRNA and to characterise the clinical significance.
  
  
  METHODS
  We established gemcitabine-resistant Panc1 cells, and induced CSC-like properties through sphere formation. Candidate miRNAs were selected through microarray analysis. The overexpression and knockdown experiments were performed by evaluating the in vitro cell growth and in vivo tumourigenicity. The expression was studied in 24 pancreatic cancer samples after laser captured microdissection and by immunohistochemical staining.
  
  
  RESULTS
  The in vitro drug sensitivity of pancreatic cancer cells was altered according to the miR-1246 expression via CCNG2. In vivo, we found that miR-1246 could increase tumour-initiating potential and induced drug resistance. A high expression level of miR-1246 was correlated with a worse prognosis and CCNG2 expression was significantly lower in those patients.
  
  
  CONCLUSIONS
  miR-1246 expression was associated with chemoresistance and CSC-like properties via CCNG2, and could predict worse prognosis in pancreatic cancer patients.
authors.affiliation: 1] Department of Gastroenterological Surgery, Osaka University, Graduate School of Medicine, 2-2, Yamadaoka, Suita, Osaka 565-0871, Japan [2] Department of Frontier Science for Cancer and Chemotherapy, Osaka University, Graduate School of Medicine, 2-2, Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Hasegawa
authors.affiliation: Department of Gastroenterological Surgery, Osaka University, Graduate School of Medicine, 2-2, Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Eguchi
authors.affiliation: Department of Gastroenterological Surgery, Osaka University, Graduate School of Medicine, 2-2, Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Nagano
authors.affiliation: Department of Frontier Science for Cancer and Chemotherapy, Osaka University, Graduate School of Medicine, 2-2, Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Konno
authors.affiliation: Department of Gastroenterological Surgery, Osaka University, Graduate School of Medicine, 2-2, Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Tomimaru
authors.affiliation: Department of Gastroenterological Surgery, Osaka University, Graduate School of Medicine, 2-2, Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Wada
authors.affiliation: Department of Gastroenterological Surgery, Osaka University, Graduate School of Medicine, 2-2, Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Hama
authors.affiliation: Department of Gastroenterological Surgery, Osaka University, Graduate School of Medicine, 2-2, Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Kawamoto
authors.affiliation: Department of Gastroenterological Surgery, Osaka University, Graduate School of Medicine, 2-2, Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Kobayashi
authors.affiliation: Department of Frontier Science for Cancer and Chemotherapy, Osaka University, Graduate School of Medicine, 2-2, Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Nishida
authors.affiliation: Department of Cancer Profiling Discovery, Osaka University, Graduate School of Medicine, 2-2, Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Koseki
authors.affiliation: Division of Molecular Therapy, Molecular Targets Laboratory, Institute of Medical Science, University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Nishimura
authors.affiliation: Division of Molecular Therapy, Molecular Targets Laboratory, Institute of Medical Science, University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Gotoh
authors.affiliation: Department of Molecular Genetics, Research Institute for Microbial Diseases, Osaka University, 3-1, Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Ohno
authors.affiliation: Department of Molecular Genetics, Research Institute for Microbial Diseases, Osaka University, 3-1, Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Yabuta
authors.affiliation: Department of Molecular Genetics, Research Institute for Microbial Diseases, Osaka University, 3-1, Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Nojima
authors.affiliation: Department of Gastroenterological Surgery, Osaka University, Graduate School of Medicine, 2-2, Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Mori
authors.affiliation: Department of Gastroenterological Surgery, Osaka University, Graduate School of Medicine, 2-2, Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Doki
authors.affiliation: 1] Department of Frontier Science for Cancer and Chemotherapy, Osaka University, Graduate School of Medicine, 2-2, Yamadaoka, Suita, Osaka 565-0871, Japan [2] Department of Cancer Profiling Discovery, Osaka University, Graduate School of Medicine, 2-2, Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Ishii
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic; D045744:Cell Line, Tumor; D056767:Cyclin G2 / Q000502:physiology*; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism*; D014411:Neoplastic Stem Cells / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; C101593:CCNG2 protein, human; D056767:Cyclin G2; C577700:MIRN1246 microRNA, human; D035683:MicroRNAs; D003841:Deoxycytidine; D000093542:Gemcitabine