The tumor suppressor microRNA-29c is downregulated and restored by celecoxib in human gastric cancer cells

Yoshimasa Saito, Hidekazu Suzuki, Hiroyuki Imaeda, Juntaro Matsuzaki, Kenro Hirata, Hitoshi Tsugawa, Sana Hibino, Yae Kanai, Hidetsugu Saito, Toshifumi Hibi

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

MicroRNAs (miRNAs) are small noncoding RNAs that function as endogenous silencers of target genes and play critical roles during carcinogenesis. The selective cyclooxygenase-2 (COX-2) inhibitor celecoxib has been highlighted as a potential drug for treatment of gastrointestinal tumors. The aim of this study was to investigate the role of miRNAs in gastric carcinogenesis and the feasibility of a new therapeutic approach for gastric cancer. miRNA expression profiles were examined in 53 gastric tumors including gastric adenomas (atypical epithelia), early gastric cancers and advanced gastric cancers and in gastric cancer cells treated with celecoxib. miRNA microarray analysis revealed that miR-29c was significantly downregulated in gastric cancer tissues relative to nontumor gastric mucosae. miR-29c was significantly activated by celecoxib in gastric cancer cells. Downregulation of miR-29c was associated with progression of gastric cancer and was more prominent in advanced gastric cancers than in gastric adenomas and early gastric cancer. In addition, expression of the oncogene Mcl-1, a target of miR-29c, was significantly increased in gastric cancer tissues relative to nontumor gastric mucosae. Activation of miR-29c by celecoxib induced suppression of Mcl-1 and apoptosis in gastric cancer cells. These results suggest that downregulation of the tumor suppressor miR-29c plays critical roles in the progression of gastric cancer. Selective COX-2 inhibitors may have clinical promise for the treatment of gastric cancer via restoration of miR-29c. What's new? MicroRNAs (miRNAs) play critical roles in carcinogenesis and may be valuable therapeutic targets for malignant disease. Here, the miRNA tumor suppressor miR-29c was found to be significantly downregulated in gastric cancer cells and to be reactivated by the selective cyclooxygenase-2 (COX-2) inhibitor celecoxib. Reactivation led to miR-29c-induced suppression of the anti-apoptotic protein Mcl-1. The data reveal that selective COX-2 inhibitors may have clinical promise for the treatment of gastric cancer via restoration of miR-29c.

Original languageEnglish
Pages (from-to)1751-1760
Number of pages10
JournalInternational Journal of Cancer
Volume132
Issue number8
DOIs
Publication statusPublished - 2013 Apr 15

    Fingerprint

Keywords

  • celecoxib
  • gastric cancer
  • Mcl-1
  • microRNA
  • miR-29c

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this