title: miR-429 determines poor outcome and inhibits pancreatic ductal adenocarcinoma growth by targeting TBK1.
abstract: BACKGROUND
  Pancreatic ductal adenocarcinoma (PDAC) ranks fourth on the list of cancer-related causes of death and its prognosis has not improved significantly over the past decades. Deregulation or dysfunction of miRNAs contribute to cancer development. Previous data indicates that miR-429 is involved in the pathogenesis of PDAC. However, the role of miR-429 in PDAC remained unknown.
  
  
  METHODS
  MiR-429 levels in sample tissues of 78 patients and in PANC1 and SW1990 cell lines were quantified by real-time PCR. MiR-429 expression was modulated using specific pre- and anti-miRNAs and cell growth was assayed by MTT analysis. Bioinformatics prediction of the miR-429 putative target genes was performed and luciferase assays confirmed TBK1 as a direct target gene. TBK1 levels in PDAC tissues were analyzed by immunohistochemistry.
  
  
  RESULTS
  MiR-429 was remarkably decreased in PDAC tissues and cell lines. Lower miR-429 expression in PDAC tissues significantly correlated with shorter survival of PDAC patients. Overexpression of miR-429 inhibited PDAC cell lines growth in vitro and vice versa. TBK1 was found to be the direct target gene of miR-429. Higher TBK1 protein level in PDAC tissues correlated with shorter survival of PDAC patients. Overexpression of TBK1 partly restored cell proliferation.
  
  
  CONCLUSIONS
  Low level of miR-429 and high level of TBK1 in PDAC promoted PDAC cells growth which might be related to the low survival rate of PDAC patients. MiR-429 play its role in PDAC by targeting TBK1.
authors.affiliation: Department of Pancreatic Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Song
authors.forename: Kailian
authors.initials: K
authors.lastname: Zheng
authors.forename: Hongyun
authors.initials: H
authors.lastname: Ma
authors.forename: Anan
authors.initials: A
authors.lastname: Liu
authors.forename: Wei
authors.initials: W
authors.lastname: Jing
authors.forename: Chenghao
authors.initials: C
authors.lastname: Shao
authors.forename: Gang
authors.initials: G
authors.lastname: Li
authors.forename: Gang
authors.initials: G
authors.lastname: Jin
mesh_terms: D020413:3' Untranslated Regions; D001483:Base Sequence; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D057809:HEK293 Cells; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D015996:Survival Rate
chemical_list: D020413:3' Untranslated Regions; C546363:MIRN429 microRNA, human; D035683:MicroRNAs; D016376:Oligonucleotides, Antisense; D017346:Protein Serine-Threonine Kinases; C403191:TBK1 protein, human