miR-26a suppresses tumor growth and metastasis by targeting FGF9 in gastric cancer

PLoS One. 2013 Aug 28;8(8):e72662. doi: 10.1371/journal.pone.0072662. eCollection 2013.

Abstract

The role of miR-26a in cancer cells seemed controversial in previous studies. Until now, the role of miR-26a in gastric cancer remains undefined. In this study, we found that miR-26a was strongly downregulated in gastric cancer (GC) tissues and cell lines, and its expression levels were associated with lymph node metastasis and clinical stage, as well as overall survival and replase-free survival of GC. We also found that ectopic expression of miR-26a inhibited GC cell proliferation and GC metastasis in vitro and in vivo. We further identified a novel mechanism of miR-26a to suppress GC growth and metastasis. FGF9 was proved to be a direct target of miR-26a, using luciferase assay and western blot. FGF9 overexpression in miR-26a-expressing cells could rescue invasion and growth defects of miR-26a. In addition, miR-26a expression inversely correlated with FGF9 protein levels in GC. Taken together, our data suggest that miR-26a functions as a tumor suppressor in GC development and progression, and holds promise as a prognostic biomarker and potential therapeutic target for GC.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / biosynthesis*
  • Biomarkers, Tumor / genetics
  • Cell Line, Tumor
  • Cell Proliferation*
  • Female
  • Fibroblast Growth Factor 9 / biosynthesis*
  • Fibroblast Growth Factor 9 / genetics
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Male
  • MicroRNAs / biosynthesis*
  • MicroRNAs / genetics
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasm Proteins / biosynthesis*
  • Neoplasm Proteins / genetics
  • RNA, Neoplasm / biosynthesis*
  • RNA, Neoplasm / genetics
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / pathology
  • Stomach Neoplasms / therapy

Substances

  • Biomarkers, Tumor
  • FGF9 protein, human
  • Fibroblast Growth Factor 9
  • MIRN26A microRNA, human
  • MicroRNAs
  • Neoplasm Proteins
  • RNA, Neoplasm

Grants and funding

This work was supported by grants from the Nature Scientific Foundation of China (81101526, 31100936) and Guangzhou Medical College Doctor Start Foundation (2012C11). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.