By downregulating TIAM1 expression, microRNA-329 suppresses gastric cancer invasion and growth

Oncotarget. 2015 Jul 10;6(19):17559-69. doi: 10.18632/oncotarget.2755.

Abstract

Gastric cancer (GC) is one of the most common malignant tumors worldwide. Emerging evidence has shown that abnormal microRNAs (miRNAs) expression is involved in tumorigenesis. MiR-329 was previously reported to act as a tumor suppressor or oncogene in some types of cancer. However, its function in gastric cancer (GC) is unclear. Here, we found that miR-329 was down-regulated in GC compared with adjacent controls. Enforced expression of miR-329 inhibited proliferation, migration and invasion of gastric cancer cells in vitro. We identified T lymphoma invasion and metastasis 1 (TIAM1) gene as potential target of miR-329. MiR-329 levels inversely correlated with TIAM1 expression in GC. Importantly, TIAM1 rescued the miR-329-mediated inhibition of cell invasion and proliferation. Finally, reintroduction of miR-329 significantly inhibited tumor formation of GC in the xenograft mice. Our findings suggest that miR-329 is a tumor suppressor and potential therapeutic target of GC.

Keywords: TIAM1; gastric cancer; miR-329; microRNAs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Down-Regulation
  • Female
  • Gene Expression Regulation, Neoplastic / genetics*
  • Guanine Nucleotide Exchange Factors / biosynthesis*
  • Guanine Nucleotide Exchange Factors / genetics
  • Heterografts
  • Humans
  • Mice
  • Mice, Nude
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Neoplasm Invasiveness / genetics*
  • Neoplasm Invasiveness / pathology
  • Real-Time Polymerase Chain Reaction
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology*
  • T-Lymphoma Invasion and Metastasis-inducing Protein 1
  • Transfection

Substances

  • Guanine Nucleotide Exchange Factors
  • MIRN329 microRNA, human
  • MicroRNAs
  • T-Lymphoma Invasion and Metastasis-inducing Protein 1
  • TIAM1 protein, human