Downregulation of CENPF Remodels Prostate Cancer Cells and Alters Cellular Metabolism

Proteomics. 2019 Jun;19(11):e1900038. doi: 10.1002/pmic.201900038. Epub 2019 May 8.

Abstract

Metabolic alterations in prostate cancer (PC) are associated with progression and aggressiveness. However, the underlying mechanisms behind PC metabolic functions are unknown. The authors' group recently reported on the important role of centromere protein F (CENPF), a protein associated with the centromere-kinetochore complex and chromosomal segregation during mitosis, in PC MRI visibility. This study focuses on discerning the role of CENPF in metabolic perturbation in human PC3 cells. A series of bioinformatics analyses shows that CENPF is one gene that is strongly associated with aggressive PC and that its expression is positively correlated with metastasis. By identifying and reconstructing the CENPF network, additional associations with lipid regulation are found. Further untargeted metabolomics analysis using gas chromatography-time-of-flight-mass spectrometry reveals that silencing of CENPF alters the global metabolic profiles of PC cells and inhibits cell proliferation, which suggests that CENPF may be a critical regulator of PC metabolism. These findings provide useful scientific insights that can be applied in future studies investigating potential targets for PC treatment.

Keywords: CENPF; metabolomics; prostate cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cell Proliferation
  • Chromosomal Proteins, Non-Histone / genetics*
  • Chromosomal Proteins, Non-Histone / metabolism
  • Down-Regulation*
  • Gene Expression Regulation, Neoplastic
  • Gene Regulatory Networks
  • Humans
  • Male
  • Metabolic Networks and Pathways
  • Microfilament Proteins / genetics*
  • Microfilament Proteins / metabolism
  • PC-3 Cells
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / metabolism
  • Transcriptome

Substances

  • Chromosomal Proteins, Non-Histone
  • Microfilament Proteins
  • centromere protein F