Knockdown of CENPK inhibits cell growth and facilitates apoptosis via PTEN-PI3K-AKT signalling pathway in gastric cancer

J Cell Mol Med. 2021 Sep;25(18):8890-8903. doi: 10.1111/jcmm.16850. Epub 2021 Aug 12.

Abstract

Previous studies have indicated that centromere protein K (CENPK) is upregulated in several cancers and related to tumorigenesis. Nevertheless, the potential function of CENPK in gastric cancer (GC) remains unknown. Here, we investigated the function of CENPK on oncogenicity and explored its underlying mechanisms in GC. Our results showed that CENPK was dramatically overexpressed in GC and was associated with poor prognosis through bioinformatics analysis. We demonstrated that CENPK is upregulated in GC tissues and cell lines. Moreover, knockdown of CENPK significantly inhibited proliferation in vitro and attenuated the growth of implanted GCs in vivo. In addition, CENPK silencing induced G1 phase cell cycle arrest and facilitated apoptosis of GC cells. KEGG pathway analysis indicated that the PI3K-AKT signalling pathway was considerably enriched. Knockdown of CENPK decreased the expression of PI3K, p-Akt (Ser437) and p-GSK3β (Ser9) in GC cells, and increased the expression of PTEN. In conclusion, this study indicated that CENPK was overexpressed in GC and may promote gastric carcinogenesis through the PTEN-PI3K-AKT signalling pathway. Thus, CENPK may be a potential target for cancer therapeutics in GC.

Keywords: CENPK; PI3K-AKT signalling pathway; PTEN; gastric cancer; proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Cell Line, Tumor
  • Cell Proliferation
  • DNA-Binding Proteins / metabolism*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Nuclear Proteins / metabolism*
  • PTEN Phosphohydrolase / metabolism*
  • Stomach Neoplasms* / metabolism
  • Stomach Neoplasms* / pathology

Substances

  • CENPK protein, human
  • DNA-Binding Proteins
  • Nuclear Proteins
  • PTEN Phosphohydrolase
  • PTEN protein, human