Suppression of CSN5 promotes the apoptosis of gastric cancer cells through regulating p53-related apoptotic pathways

Bioorg Med Chem Lett. 2015 Aug 1;25(15):2897-901. doi: 10.1016/j.bmcl.2015.05.057. Epub 2015 May 29.

Abstract

As one of the COP9 signalosome complex, CSN5 (also known as Jab1) has been confirmed overexpression in many human cancers and affected multiple pathways associating with cell proliferation and apoptosis. Correlation of CSN5 overexpression with poor prognosis for cancer provides evidence that it is involved in the tumorigenesis. However, little is known about the functional role and the underlying mechanism of CSN5 in gastric cancer progression. In the current study, the effect of CSN5 siRNA (small-interfering RNA) on the proliferation and apoptosis of human gastric cancer cells (AGS and MKN45) were examined. Our results showed that knockdown of CSN5 could inhibit proliferation and promote apoptosis of gastric cancer cells. Additionally, suppression of CSN5 expression contributed to the increased expression levels of p53 and Bax. In conclusion, CSN5 overexpression is significantly correlated with gastric cancer progression, and CSN5 could be a novel target in gastric cancer therapy.

Keywords: Apoptosis; CSN5/Jab1; Gastric cancer; Proliferation; p53; siRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis*
  • COP9 Signalosome Complex
  • Cell Line, Tumor
  • Gastric Mucosa / metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Peptide Hydrolases / genetics*
  • RNA Interference
  • RNA, Small Interfering / genetics
  • Signal Transduction
  • Stomach / pathology*
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / pathology*
  • Tumor Suppressor Protein p53 / genetics*
  • bcl-2-Associated X Protein / genetics

Substances

  • Intracellular Signaling Peptides and Proteins
  • RNA, Small Interfering
  • Tumor Suppressor Protein p53
  • bcl-2-Associated X Protein
  • Peptide Hydrolases
  • COPS5 protein, human
  • COP9 Signalosome Complex