Clinical significance of miR-146a in gastric cancer cases

Ryunosuke Kogo, Koshi Mimori, Fumiaki Tanaka, Shizuo Komune, Masaki Mori

Research output: Contribution to journalArticle

163 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)4277-4284
Number of pages8
JournalClinical Cancer Research
Volume17
Issue number13
DOIs
Publication statusPublished - Jul 1 2011

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Stomach Neoplasms
Epidermal Growth Factor Receptor
Single Nucleotide Polymorphism
Prostatic Neoplasms
Seeds
Interleukin-1 Receptor-Associated Kinases
Genotype
Breast Neoplasms
MicroRNAs
Pancreatic Neoplasms
DNA Sequence Analysis
Real-Time Polymerase Chain Reaction
Neoplasms
Research Design
Down-Regulation
Lymph Nodes
Neoplasm Metastasis
Genes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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Clinical significance of miR-146a in gastric cancer cases. / Kogo, Ryunosuke; Mimori, Koshi; Tanaka, Fumiaki; Komune, Shizuo; Mori, Masaki.

In: Clinical Cancer Research, Vol. 17, No. 13, 01.07.2011, p. 4277-4284.

Research output: Contribution to journalArticle

Kogo, Ryunosuke ; Mimori, Koshi ; Tanaka, Fumiaki ; Komune, Shizuo ; Mori, Masaki. / Clinical significance of miR-146a in gastric cancer cases. In: Clinical Cancer Research. 2011 ; Vol. 17, No. 13. pp. 4277-4284.
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AB - 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.

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