title: Metformin alters the expression profiles of microRNAs in human pancreatic cancer cells.
abstract: OBJECTIVE
  To investigate the effect of metformin on the expression profiles of microRNAs in human pancreatic cancer cells.
  
  
  METHODS
  MicroRNAs real-time PCR Array was applied to investigate differentially expressed miRNAs in Sw1990 cells treated with or without metformin. Stem-loop real time RT-PCR was used to confirm the results of the array assay in Sw1990 and Panc-1 cells. The effects of miR-26a on cell growth, apoptosis, invasion and migration abilities were respectively examined by CCK8 assay, Apoptosis assay, Matrigel invasion and migration assay. HMGA1 was proved to be a target of miR-26a by Luciferase reporter assay, Real-time PCR and Western-blotting.
  
  
  RESULTS
  Nine miRNAs were significantly up-regulated in metformin treated cells. Metformin up-regulated the expression of miR-26a, miR-192 and let-7c in a dose-dependent manner. Forced expression of miR-26a significantly inhibited cell proliferation, invasion, migration and increased cell apoptosis, whereas knockdown of miR-26a obtained the opposite effect. Furthermore, we demonstrated that HMGA1, an oncogene, is a direct target of miR-26a. Nude mice xenograft models confirmed that metformin up-regulated the level of miR-26a and surpressed the expression of HMGA1 in vivo.
  
  
  CONCLUSIONS
  These observations suggested that modulation of miRNA expression may be an important mechanism underlying the biological effects of metformin.
authors.affiliation: Department of Gastroenterology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197 Ruijin Second Road, Shanghai 200025, PR China.
authors.forename: Weiguang
authors.initials: W
authors.lastname: Li
authors.forename: Yaozong
authors.initials: Y
authors.lastname: Yuan
authors.forename: Liya
authors.initials: L
authors.lastname: Huang
authors.forename: Minmin
authors.initials: M
authors.lastname: Qiao
authors.forename: Yongping
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics; D006801:Humans; D008687:Metformin / Q000494:pharmacology* / Q000627:therapeutic use*; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays
chemical_list: D008687:Metformin; D035683:MicroRNAs; C546783:MIRN192 microRNA, human; C528163:MIRN26 microRNA, human