Identification of new octamer transcription factor 1-target genes upregulated in castration-resistant prostate cancer

Cancer Sci. 2019 Nov;110(11):3476-3485. doi: 10.1111/cas.14183. Epub 2019 Sep 16.

Abstract

Octamer transcription factor 1 (OCT1) is an androgen receptor (AR)-interacting partner and regulates the expression of target genes in prostate cancer cells. However, the function of OCT1 in castration-resistant prostate cancer (CRPC) is not fully understood. In the present study, we used 22Rv1 cells as AR-positive CRPC model cells to analyze the role of OCT1 in CRPC. We showed that OCT1 knockdown suppressed cell proliferation and migration of 22Rv1 cells. Using microarray analysis, we identified four AR and OCT1-target genes, disks large-associated protein 5 (DLGAP5), kinesin family member 15 (KIF15), non-SMC condensin I complex subunit G (NCAPG), and NDC80 kinetochore complex component (NUF2) in 22Rv1 cells. We observed that knockdown of DLGAP5 and NUF2 suppresses growth and migration of 22Rv1 cells. Furthermore, immunohistochemical analysis showed that positive expression of DLGAP5 in prostate cancer specimens is related to poor cancer-specific survival rates of patients. Notably, enhanced expression of DLGAP5 was observed in CRPC tissues of patients. Thus, our findings suggest that these four genes regulated by the AR/OCT1 complex could have an important role in CRPC progression.

Keywords: CRPC; DLGAP5; OCT1; androgen receptor; prostate cancer.

MeSH terms

  • Aged
  • Cell Cycle Proteins / genetics*
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Cytoskeletal Proteins
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Gene Silencing
  • Humans
  • Kinesins / genetics*
  • Male
  • Microarray Analysis
  • Neoplasm Proteins / genetics*
  • Nuclear Proteins / genetics
  • Octamer Transcription Factor-1 / genetics
  • Octamer Transcription Factor-1 / physiology*
  • Prostatic Neoplasms, Castration-Resistant / genetics*
  • Prostatic Neoplasms, Castration-Resistant / mortality
  • Receptors, Androgen / genetics*
  • Receptors, Androgen / metabolism
  • Survival Rate
  • Up-Regulation

Substances

  • Cell Cycle Proteins
  • Cytoskeletal Proteins
  • DLGAP5 protein, human
  • KIF15 protein, human
  • NCAPG protein, human
  • NDC80 protein, human
  • NUF2 protein, human
  • Neoplasm Proteins
  • Nuclear Proteins
  • Octamer Transcription Factor-1
  • POU2F1 protein, human
  • Receptors, Androgen
  • Kinesins