title: Modulation of FoxO1 expression by miR-21 to promote growth of pancreatic ductal adenocarcinoma.
abstract: BACKGROUND
  Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal primary tumors in humans, with undetermined tumorigenesis. Although previous work by us, and by others, has clearly demonstrated an involvement of miR-21 in the growth of PDAC, the underlying mechanism has not been clarified.
  
  
  METHODS
  Here we analyzed the regulation of FoxO1 by miR-21 in vitro and in vivo, using luciferase-reporter assay and pancreatic intraductal infusion of antisense of miR-21, respectively.
  
  
  RESULTS
  We found that overexpression of miR-21 in PDAC cells decreased FoxO1 protein levels, whereas inhibition of miR-21 increased FoxO1 levels. Further, miR-21 bound to FoxO1 mRNA to prevent its translation through its 3'UTR. Moreover, administration of antisense of miR-21 through an intraductal infusion system significantly decreased miR-21 levels and increased FoxO1 levels in implanted PDAC, resulting in a significant decrease in PDAC growth.
  
  
  CONCLUSIONS
  Taken together, our data highlight miR-21/FoxO1 axis as a novel therapeutic target for inhibiting the growth of PDAC.
authors.affiliation: Department of Medical Oncology, Shanghai First People's Hospital, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Weifeng
authors.initials: W
authors.lastname: Song
authors.forename: Qi
authors.initials: Q
authors.lastname: Li
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Liwei
authors.initials: L
authors.lastname: Wang
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D001483:Base Sequence; D021441:Carcinoma, Pancreatic Ductal / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D011859:Radiography; D016415:Sequence Alignment; D014162:Transfection; D014183:Transplantation, Heterologous
chemical_list: D020413:3' Untranslated Regions; C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D016376:Oligonucleotides, Antisense