MicroRNA-134 suppresses cell proliferation in gastric cancer cells via targeting of GOLPH3

Oncol Rep. 2017 Apr;37(4):2441-2448. doi: 10.3892/or.2017.5488. Epub 2017 Mar 2.

Abstract

Emerging evidence has shown that microRNAs (miRNAs) play critical roles in tumor development and progression. miR-134 has been found to act as a tumor-suppressor in numerous types of cancers. However, little is known concerning the potential role of miR-134 in gastric carcinogenesis. In the present study, we found that miR-134 was highly downregulated in gastric cancer tissues and cell lines when compared with levels in their adjacent non-tumor tissues and the normal human gastric epithelial cell line GES-1. Additionally, overexpression of miR-134 was accompanied by reduced cell proliferation in vitro and decreased tumor size in vivo. Further investigation by luciferase reporter assay indicated that Golgi phosphoprotein 3 (GOLPH3), a potent oncogene, was a direct target of miR-134. The activity of a luciferase reporter carrying the miR-134 binding site in the 3'-untranslated region (3'-UTR) of GOLPH3 was repressed by overexpression of miR-134, while a mutation in the 3'-UTR of GOLPH3 abrogated this effect, indicating that GOLPH3 is a target gene of miR-134. Overexpression of GOLPH3 blocked the antiproliferative effect of pre-miR-134 in gastric carcinoma cells. Furthermore, overexpression of miR-134 was associated with decreased phosphorylation of AKT, mTOR and S6K. Taken together, these data suggest that miR-134 regulates gastric cancer cell proliferation, at least potentially, through downregulation of the GOLPH3 gene, implicating a candidate tumor-suppressor miRNA in the pathogenesis of gastric cancer.

MeSH terms

  • 3' Untranslated Regions
  • Animals
  • Cell Line, Tumor
  • Cell Proliferation
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Membrane Proteins / genetics*
  • Mice
  • MicroRNAs / genetics*
  • Neoplasm Transplantation
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / pathology*

Substances

  • 3' Untranslated Regions
  • GOLPH3 protein, human
  • MIRN134 microRNA, human
  • Membrane Proteins
  • MicroRNAs