CSN5/Jab1 facilitates non-small cell lung cancer cell growth through stabilizing survivin

Biochem Biophys Res Commun. 2018 Jun 2;500(2):132-138. doi: 10.1016/j.bbrc.2018.03.183. Epub 2018 Apr 19.

Abstract

CSN5/JAB1 is a critical subunit of the COP9 signalosome (CSN) and is essentially involved in diverse types of cancer, but little is known about the role of CSN5 in non-small cell lung cancer (NSCLC). In the current study, we found that CSN5 expression was higher in NSCLC tissues compared to the corresponding non-tumor tissues. High CSN5 expression level is closely correlated with tumor progression and poor survival in NSCLC patients. We also found that knockdown of CSN5 remarkably suppressed cell growth by inducing cell cycle arrest and apoptosis promotion in NSCLC cells. Mechanistic investigations revealed that CSN5 directly bound survivin and decreased its ubiquitination to enhance the protein stability of survivin. Additionally, our results confirmed that the tumor-promoting effects of CSN5 in NSCLC cells is at least partly through stabilization of survivin. Overall, our data suggested that CSN5 functions as an oncogenic gene in NSCLC, which could be a potential diagnostic and therapeutic target for NSCLC.

Keywords: CSN5/Jab1; Non-small cell lung cancer; Survivin; Ubiquitination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • COP9 Signalosome Complex / metabolism*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Cell Cycle / genetics
  • Cell Line, Tumor
  • Cell Proliferation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Humans
  • Inhibitor of Apoptosis Proteins / metabolism*
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology*
  • Male
  • Mice, Inbred BALB C
  • Mice, Nude
  • Middle Aged
  • Pancreatic Neoplasms / pathology
  • Peptide Hydrolases / metabolism*
  • Protein Binding
  • Protein Stability
  • Proteolysis
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism
  • Survivin
  • Ubiquitination
  • Up-Regulation / genetics

Substances

  • BIRC5 protein, human
  • Inhibitor of Apoptosis Proteins
  • Intracellular Signaling Peptides and Proteins
  • NEAT1 long non-coding RNA, human
  • RNA, Long Noncoding
  • Survivin
  • Peptide Hydrolases
  • COPS5 protein, human
  • COP9 Signalosome Complex