miR-135a inhibits tumor metastasis and angiogenesis by targeting FAK pathway

Oncotarget. 2017 May 9;8(19):31153-31168. doi: 10.18632/oncotarget.16098.

Abstract

Tumor metastasis has been the major cause of recurrence and death in patients with gastric cancer. Here, we find miR-135a has a decreased expression in the metastatic cell lines compared with its parental cell lines by analyzing microRNA array. Further results show that miR-135a is downregulated in the majority of human gastric cancer tissues and cell lines. Decreased expression of miR-135a is associated with TNM stage and poor survival. Besides, regaining miR-135a in gastric cancer cells obviously inhibits tumor growth, migration, invasion and angiogenesis by targeting focal adhesion kinase (FAK) pathway. Bioinformatics analysis and molecular experiments further prove that miR-135a is a novel downstream gene of tumor suppressor p53. Blocking FAK with its inhibitor can also enhance miR-135a expression through inducing p53. In summary, this study reveals the expression and function of miR-135a in gastric cancer and uncovers a novel regulatory mechanism of miR-135a.

Keywords: FAK; gastric cancer; metastasis; miR-135a; p53.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Disease Models, Animal
  • Female
  • Focal Adhesion Protein-Tyrosine Kinases / genetics*
  • Focal Adhesion Protein-Tyrosine Kinases / metabolism
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Heterografts
  • Humans
  • Mice
  • Mice, Knockout
  • MicroRNAs / genetics*
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Neoplasms / genetics*
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Neovascularization, Pathologic / genetics*
  • RNA Interference
  • Signal Transduction*
  • Tumor Suppressor Protein p53 / genetics

Substances

  • MIRN135 microRNA, human
  • MicroRNAs
  • Tumor Suppressor Protein p53
  • Focal Adhesion Protein-Tyrosine Kinases