UBE2T knockdown inhibits gastric cancer progression

Oncotarget. 2017 May 16;8(20):32639-32654. doi: 10.18632/oncotarget.15947.

Abstract

Ubiquitin-conjugating enzymes (E2 enzymes) such as UBE2T target proteins for degradation via the proteasome. Here, we examined the effects of UBE2T on the progression of gastric cancer. UBE2T was highly expressed in gastric tumors and gastric cancer cells. siRNA-mediated suppression of UBE2T inhibited gastric cancer cell proliferation and colony formation by promoting cell cycle arrest at G2/M phase and increasing apoptosis. Suppression of UBE2T also attenuated the invasive and metastatic abilities of gastric cancer cells by altering expression of epithelial-mesenchymal transition (EMT)-related factors. A xenograft model in which nude mice were injected with UBE2T knockdown human gastric cancer cells confirmed that suppression of UBE2T also decreased tumor formation and growth in vivo. Expression levels of CCND1, Phospho-GSK3B, WNT family members, and MYC were all affected by UBE2T knockdown. These results suggest that UBE2T plays a critical role in gastric cancer, and that it may serve as a useful prognostic biomarker and therapeutic target in gastric cancer patients.

Keywords: UBE2T; gastric cancer; invasion and metastasis; tumor apoptosis; ubiquitination.

MeSH terms

  • Animals
  • Cell Cycle
  • Cell Line, Tumor
  • Cell Proliferation
  • Cell Survival
  • Disease Progression
  • Epithelial-Mesenchymal Transition
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques*
  • Gene Regulatory Networks
  • Humans
  • Mice
  • Mice, Nude
  • Neoplasm Transplantation
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology*
  • Ubiquitin-Conjugating Enzymes / genetics*
  • Ubiquitin-Conjugating Enzymes / metabolism*
  • Up-Regulation

Substances

  • UBE2T protein, human
  • Ubiquitin-Conjugating Enzymes