MicroRNA-148a is downregulated in gastric cancer, targets MMP7, and indicates tumor invasiveness and poor prognosis
Article first published online: 6 JAN 2014
© 2013 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
Volume 105, Issue 2, pages 236–243, February 2014
How to Cite
Cancer Sci 105 (2014) 236–243
Ministry of Education, Culture, Science, Sports, and Technology of Japan; Ministry of Health, Labor and Welfare of Japan; The National Institute of Biomedical Innovation; the Japan Society for the Promotion of Science; the National Cancer Center Research and Development Fund.
- Issue published online: 10 FEB 2014
- Article first published online: 6 JAN 2014
- Accepted manuscript online: 27 NOV 2013 10:11AM EST
- Manuscript Accepted: 26 NOV 2013
- Manuscript Revised: 16 NOV 2013
- Manuscript Received: 20 AUG 2013
- Ministry of Education, Culture, Science, Sports, and Technology of Japan
- Ministry of Health, Labor, and Welfare of Japan
- National Institute of Biomedical Innovation
- Japan Society for the Promotion of Science
- National Cancer Center Research and Development Fund. Grant Number: 23-A-9
- Gastric cancer;
- cancer invasion
Gastric cancer (GC) develops through deregulation of gene expression and accumulation of epigenetic abnormalities, leading to tumor cell acquisition of malignant features. MicroRNAs (miRNAs) play a critical role in cancer development where they can act as oncogenes or oncosuppressors. To identify miRNAs that are associated with some clinicopathologic features of GC and/or participate in tumor progression, miRNA expression in 20 GC tissues and five corresponding non-neoplastic gastric mucosa was examined by miRNA microarray. Oligonucleotide array analysis was carried out for miRNA target prediction. The functions of candidate miRNAs and their target genes were also analyzed by quantitative RT-PCR, Western blotting, reporter gene assay, and cell invasion assay. Comparison of miRNA expression profiles revealed that downregulation of miR-148a was identified in most of the GC tissues. Downregulation of miR-148a was significantly correlated with an advanced clinical stage, lymph node metastasis, and poor clinical outcome. Custom oligonucleotide array analysis revealed that MMP7 expression was markedly downregulated in miR-148a-overexpressing GC cells; MMP7 was found to be a direct and functional target of miR-148a, participating in cell invasion. These results suggest that miR-148a contributes to the maintenance of homeostasis in normal stomach tissue and plays an important role in GC invasion by regulating MMP7 expression.