title: Clinical significance of miR-146a in gastric cancer cases.
abstract: OBJECTIVE
  The profiles of microRNAs change significantly in gastric cancer. MiR-146a is reported to be a tumor suppressor in pancreatic cancer, breast cancer, and prostate cancer. We investigated the clinical significance of miR-146a in gastric cancer, in particular focusing on hypothetical miR-146a target genes, such as epidermal growth factor receptor (EGFR) and interleukin-1 receptor-associated kinase (IRAK1).
  
  
  METHODS
  We examined miR-146a levels in 90 gastric cancer samples by q-real-time (qRT)-PCR and analyzed the association between miR-146a levels and clinicopathologic factors and prognosis. The regulation of EGFR and IRAK1 by miR-146a was examined with miR-146a-transfected gastric cancer cells. Moreover, we analyzed the association between miR-146a levels and the G/C single nucleotide polymorphism (SNP) within pre-miR-146a seed sequences in 76 gastric cancer samples, using direct sequencing of genomic DNA.
  
  
  RESULTS
  In 90 clinical samples of gastric cancer, miR-146a levels in cancer tissues were significantly lower than those in the corresponding noncancerous tissue (P < 0.001). Lower levels of miR-146a were associated with lymph node metastasis and venous invasion (P < 0.05). Moreover, a lower level of miR-146a was an independent prognostic factor for overall survival (P = 0.003). Ectopic expression of miR-146a inhibited migration and invasion and downregulated EGFR and IRAK1 expression in gastric cancer cells. In addition, G/C SNP within the pre-miR-146a seed sequence significantly reduced miR-146a levels in the GG genotype compared with the CC genotype.
  
  
  CONCLUSIONS
  MiR-146a contains an SNP, which is associated with mature miR-146a expression. MiR-146a targeting of EGFR and IRAK1 is an independent prognostic factor in gastric cancer cases.
authors.affiliation: Department of Surgical Oncology, Medical Institute of Bioregulation, Kyushu University, Beppu, Japan.
authors.forename: Ryunosuke
authors.initials: R
authors.lastname: Kogo
authors.forename: Koshi
authors.initials: K
authors.lastname: Mimori
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Tanaka
authors.forename: Shizuo
authors.initials: S
authors.lastname: Komune
authors.forename: Masaki
authors.initials: M
authors.lastname: Mori
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D009361:Neoplasm Invasiveness / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011379:Prognosis; D013274:Stomach Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000503:physiopathology*; D016019:Survival Analysis
chemical_list: C542542:MIRN146 microRNA, human; D035683:MicroRNAs