title: MiR-204 down-regulation elicited perturbation of a gene target signature common to human cholangiocarcinoma and gastric cancer.
abstract: OBJECTIVE
  There is high need of novel diagnostic and prognostic tools for tumors of the digestive system, such as gastric cancer and cholangiocarcinoma. We recently found that miR-204 was deeply downregulated in gastric cancer tissues. Here we investigated whether this was common to other tumors of the digestive system and whether this elicited a miR-204-dependent gene target signature, diagnostically and therapeutically relevant. Finally, we assessed the contribution of the identified target genes to the cell cycle progression and clonogenicity of gastric cancer and cholangiocarcinoma cell lines.
  
  
  METHODS
  We employed quantitative PCR and Affymetrix profiling for gene expression studies. In silico analysis aided us to identifying a miR-204 target signature in publicly available databases (TGCA). We employed transient transfection experiments, clonogenic assays and cell cycle profiling to evaluate the biological consequences of miR-204 perturbation.
  
  
  RESULTS
  We identified a novel miR-204 gene target signature perturbed in gastric cancer and in cholangiocarcinoma specimens. We validated its prognostic relevance and mechanistically addressed its biological relevance in GC and CC cell lines.
  
  
  CONCLUSIONS
  We suggest that restoring the physiological levels of miR-204 in some gastrointestinal cancers might be exploited therapeutically.
authors.affiliation: Oncogenomic and Epigenetic Unit, Italian National Cancer Institute 'Regina Elena', Rome, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Canu
authors.affiliation: Oncogenomic and Epigenetic Unit, Italian National Cancer Institute 'Regina Elena', Rome, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Sacconi
authors.affiliation: Faculty of Medicine and Psychology, Surgical and Medical Department of Clinical Sciences, Biomedical Technologies and Translational Medicine, University of Rome 'La Sapienza', Sant'Andrea Hospital, Rome, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Lorenzon
authors.affiliation: Oncogenomic and Epigenetic Unit, Italian National Cancer Institute 'Regina Elena', Rome, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Biagioni
authors.affiliation: Oncogenomic and Epigenetic Unit, Italian National Cancer Institute 'Regina Elena', Rome, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Lo Sardo
authors.affiliation: Department of Research, Advanced Diagnostic, and Technological Innovation, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Diodoro
authors.affiliation: Department of Oncology, Juravinski Cancer Center, McMaster University Hamilton, Hamilton, Ontario, Canada.
authors.forename: Paola
authors.initials: P
authors.lastname: Muti
authors.affiliation: HepatoBiliary Pancreatic Surgery, 'Regina Elena' National Cancer Institute, Rome, Italy.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Garofalo
authors.affiliation: Department of Oncology, Juravinski Cancer Center, McMaster University Hamilton, Hamilton, Ontario, Canada.|Molecular Chemoprevention Group, Italian National Cancer Institute 'Regina Elena', Rome, Italy.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Strano
authors.affiliation: Department of Medical and Surgical Sciences, Pathology Unit, S. Orsola-Malpighi Hospital, Alma Mater Studiorum, University of Bologna, Bologna, Italy.
authors.forename: Antonietta
authors.initials: A
authors.lastname: D'Errico
authors.affiliation: HepatoBiliary Pancreatic Surgery, 'Regina Elena' National Cancer Institute, Rome, Italy.
authors.forename: Gian Luca
authors.initials: GL
authors.lastname: Grazi
authors.affiliation: Oncogenomic and Epigenetic Unit, Italian National Cancer Institute 'Regina Elena', Rome, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Cioce
authors.affiliation: Oncogenomic and Epigenetic Unit, Italian National Cancer Institute 'Regina Elena', Rome, Italy.|Department of Oncology, Juravinski Cancer Center, McMaster University Hamilton, Hamilton, Ontario, Canada.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Blandino
mesh_terms: D001650:Bile Duct Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D018281:Cholangiocarcinoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D019295:Computational Biology / Q000379:methods; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D063990:Gene Ontology; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D059467:Transcriptome
chemical_list: C549404:MIRN204 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger
keywords: cholangiocarcinoma; gastric cancer; micro-RNA, miR-204, prognostic