Epigenetic repression of microRNA-129-2 leads to overexpression of SOX4 in gastric cancer

Biochem Biophys Res Commun. 2010 Apr 16;394(4):1047-52. doi: 10.1016/j.bbrc.2010.03.121. Epub 2010 Mar 21.

Abstract

High levels of SOX4 expression have been found in a variety of human cancers, such as lung, brain and breast cancers. However, the expression of SOX4 in gastric tissues remains unknown. The SOX4 expression was detected using immunohistochemical staining and semi-quantitative RT-PCR, and our results showed that SOX4 was up-regulated in gastric cancer compared to benign gastric tissues. To further elucidate the molecular mechanisms underlying up-regulation of SOX4 in gastric cancers, we analyzed the expression of microRNA-129-2 (miR-129-2) gene, the epigenetic repression of which leads to overexpression of SOX4 in endometrial cancer. We found that up-regulation of SOX4 was inversely associated with the epigenetic silencing of miR-129-2 in gastric cancer, and restoration of miR-129-2 down-regulated SOX4 expression. We also found that inactivation of SOX4 by siRNA and restoration of miR-129-2 induced apoptosis in gastric cancer cells.

MeSH terms

  • Apoptosis / genetics
  • DNA Methylation
  • Down-Regulation
  • Epigenesis, Genetic*
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neoplasm Metastasis
  • Prognosis
  • SOXC Transcription Factors / genetics*
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / mortality
  • Stomach Neoplasms / pathology*
  • Up-Regulation

Substances

  • MicroRNAs
  • Mirn129 microRNA, human
  • SOX4 protein, human
  • SOXC Transcription Factors