Clinical significance of miR-146a in gastric cancer cases

Clin Cancer Res. 2011 Jul 1;17(13):4277-84. doi: 10.1158/1078-0432.CCR-10-2866. Epub 2011 Jun 1.


Purpose: 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).

Experimental design: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Movement / genetics
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism*
  • Neoplasm Invasiveness / genetics
  • Polymorphism, Single Nucleotide / genetics
  • Prognosis
  • Stomach Neoplasms / diagnosis
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / mortality
  • Stomach Neoplasms / physiopathology*
  • Survival Analysis


  • MIRN146 microRNA, human
  • MicroRNAs