title: Knockdown of microRNA-21 inhibits proliferation and increases cell death by targeting programmed cell death 4 (PDCD4) in pancreatic ductal adenocarcinoma.
abstract: OBJECTIVE
  This study aims to examine the expression of a panel of five microRNAs (miRNA) in pancreatic ductal adenocarcinoma (PDAC) and the functional effect of miR-21 inhibition in PDAC cell lines.
  
  
  BACKGROUND
  miRNA are short, non-coding RNA molecules, which play important roles in several cellular processes by silencing expression of their target genes through translational repression or mRNA degradation. They are often aberrantly expressed in cancer, and this dysregulation can promote carcinogenesis by altering the expression of tumour suppressor or oncogenes.
  
  
  METHODS
  miRNA expression levels were measured in 24 PDAC tumour/matched adjacent normal tissue samples and three PDAC cell lines using reverse transcription polymerase chain reaction. Levels of cell proliferation and death and expression of programmed cell death 4 (PDCD4; tumour suppressor) were studied in PDAC cells (MIA-Pa-Ca-2) in the absence or presence of a miR-21 inhibitor.
  
  
  RESULTS
  PDAC primary tissues and cell lines displayed a consistent upregulation of miR-21 (P < 0.0001) and downregulation of both miR-148a (P < 0.0001) and miR-375 (P < 0.0001) relative to adjacent normal tissue. Furthermore, miR-21 levels in the primary tumours correlated with disease stage (P < 0.0001). Inhibition of miR-21 in MIA-Pa-Ca-2 PDAC cells led to reduced cell proliferation (P < 0.01) and increased cell death (P < 0.01), with simultaneous increase in levels of the tumour suppressor, PDCD4 (P < 0.01).
  
  
  CONCLUSIONS
  miRNA expression profiles may be used as biomarkers for detecting pancreatic cancer. Moreover, miR-21 could be a predictor of disease progression and a possible therapeutic target in part by upregulating PDCD4 in pancreatic cancer.
authors.affiliation: Division of Surgery, School of Graduate Entry Medicine and Health, University of Nottingham Medical School at Derby, Royal Derby Hospital, Uttoxeter Road, Derby, DE22 3DT, UK. imran.bhatti@nhs.net
authors.forename: Imran
authors.initials: I
authors.lastname: Bhatti
authors.forename: Andrew
authors.initials: A
authors.lastname: Lee
authors.forename: Victoria
authors.initials: V
authors.lastname: James
authors.forename: Richard I
authors.initials: RI
authors.lastname: Hall
authors.forename: Jonathan N
authors.initials: JN
authors.lastname: Lund
authors.forename: Cristina
authors.initials: C
authors.lastname: Tufarelli
authors.forename: Dileep N
authors.initials: DN
authors.lastname: Lobo
authors.forename: Michael
authors.initials: M
authors.lastname: Larvin
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis / Q000235:genetics; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics* / Q000473:pathology; D016923:Cell Death / Q000235:genetics*; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques / Q000379:methods*; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology; D016601:RNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: D051017:Apoptosis Regulatory Proteins; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; C114487:PDCD4 protein, human; D016601:RNA-Binding Proteins