title: MicroRNA miR-548d is a superior regulator in pancreatic cancer.
abstract: OBJECTIVE
  This study aimed to identify microRNAs as novel biomarkers for improved diagnosis, prognosis prediction, and as a therapeutic target for pancreatic cancer. microRNAs may have a general role by acting as superordinated key regulators of tumorigenesis.
  
  
  METHODS
  Individual cellular molecules of multiple pathways associated with pancreatic cancer were analyzed for common microRNA binding sites, thereby enabling the identification of key regulating microRNAs. The potential of the identified microRNAs was subsequently determined in cell culture experiments.
  
  
  RESULTS
  Using bioinformatic pathway analyses, miR-548d was identified to target multiple components of pancreatic cancer-related pathways. The effect of microRNA on pancreatic cells was determined by overexpression studies using PANC-1 cells, resulting in impaired cell proliferation because of increased apoptosis and cell cycle arrest. In addition, miR-548d overexpression led to a sensitization to gemcitabine.
  
  
  CONCLUSIONS
  MicroRNA miR-548d was identified as a potential superior regulator for the development and progression of pancreatic cancer by targeting multiple factors of crucial pathways. Therapeutically, microRNAs with superordinate function, such as miR-548d, may be promising diagnostic and therapeutic tools for the future treatment of pancreatic cancer.
authors.affiliation: Institute of Cell and Molecular Pathology, Hannover Medical School, Hannover, Germany. holger_heyn@yahoo.de
authors.forename: Holger
authors.initials: H
authors.lastname: Heyn
authors.forename: Sabine
authors.initials: S
authors.lastname: Schreek
authors.forename: Reena
authors.initials: R
authors.lastname: Buurman
authors.forename: Tim
authors.initials: T
authors.lastname: Focken
authors.forename: Brigitte
authors.initials: B
authors.lastname: Schlegelberger
authors.forename: Carmela
authors.initials: C
authors.lastname: Beger
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001665:Binding Sites; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D019295:Computational Biology; D030541:Databases, Genetic; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D014162:Transfection; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; C561887:MIRN548 microRNA, human; D035683:MicroRNAs; D003841:Deoxycytidine; D000093542:Gemcitabine