MicroRNA-143 regulates collagen type III expression in stromal fibroblasts of scirrhous type gastric cancer
Article first published online: 8 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 228–235, February 2014
How to Cite
Cancer Sci 105 (2014) 228–235
Ministry of Education, Culture, Science, Sports, and Technology of Japan. Ministry of Health, Labour and Welfare of Japan. The National Institute of Biomedical Innovation. Japan Society for the Promotion of Science. National Cancer Center Research and Development Fund.
- Issue published online: 10 FEB 2014
- Article first published online: 8 JAN 2014
- Accepted manuscript online: 27 NOV 2013 10:11AM EST
- Manuscript Accepted: 26 NOV 2013
- Manuscript Revised: 24 NOV 2013
- Manuscript Received: 16 JUL 2013
- Ministry of Education, Culture, Science, Sports, and Technology of Japan
- Ministry of Health, Labour and Welfare of Japan
- The National Institute of Biomedical Innovation
- Japan Society for the Promotion of Science
- National Cancer Center Research and Development. Grant Number: 23-A-9
- Collagen type III;
- gastric cancer;
- transforming growth factor-β
Gastric cancer (GC) is one of the most common malignancies worldwide. In particular, scirrhous type GC is highly metastatic and is characterized clinically by rapid disease progression and poor prognosis. MicroRNAs (miRNAs) play crucial roles in cancer development and progression. In the present study, we identified several miRNAs that are expressed at higher levels in scirrhous type GC than in non-scirrhous type GC by miRNA microarray analysis. Among these, microRNA-143 (miR-143) expression was higher in scirrhous type GC than in non-scirrhous types of GC. In situ hybridization and quantitative RT-PCR analysis showed that miR-143 is expressed by stromal fibroblasts but not by cancer cells. In stromal cells, miR-143 enhanced collagen type III expression in normal gastric fibroblasts and cancer-associated fibroblasts through activation of transforming growth factor-β)/SMAD signaling. Furthermore, high miR-143 expression in GC was associated with worse cancer-specific mortality (P = 0.0141). Multivariate analysis revealed that miR-143 was an independent prognostic factor. Treatment of GC cell lines with 5-aza-2′-deoxycytidine restored the expression of miR-143, and precursor miR-143 caused the inhibition of cancer cell invasion. These data suggest that miR-143 regulates fibrosis of scirrhous type GC through induction of collagen expression in stromal fibroblasts and that miR-143 expression serves as a prognostic marker of GC.