USP14 de-ubiquitinates vimentin and miR-320a modulates USP14 and vimentin to contribute to malignancy in gastric cancer cells

Oncotarget. 2017 Jul 25;8(30):48725-48736. doi: 10.18632/oncotarget.10706.

Abstract

Vimentin plays important roles in the epithelial-to-mesenchymal transition (EMT). In this study, we found that vimentin was highly expressed in human gastric cancer (GC) tissues and cell lines and significantly promoted cell growth, migration and invasion. Ubiquitin-specific protease 14 (USP14) interacted with the vimentin protein, which led to its de-ubiquitination. miR-320a was found to bind to the 3'UTR of both vimentin and USP14 transcripts and downregulate the expression of both proteins. The downregulation of miR-320a upregulates vimentin expression by directly binding to the 3'UTR of vimentin to derepress expression and indirectly by augmenting USP14 to increase vimentin stability in GC cells. Taken together, these results provide new insight into malignancy in gastric cancers.

Keywords: USP14; gastric cancer; miR-320a; vimentin.

MeSH terms

  • 3' Untranslated Regions
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Cell Survival / genetics
  • Disease Progression
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MicroRNAs / genetics*
  • RNA Interference
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / pathology
  • Ubiquitin Thiolesterase / metabolism*
  • Ubiquitination
  • Vimentin / metabolism*

Substances

  • 3' Untranslated Regions
  • MIRN320 microRNA, human
  • MicroRNAs
  • USP14 protein, human
  • Vimentin
  • Ubiquitin Thiolesterase