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

Shinichiro Yamamoto1,2, Ken-Ichi Takayama1, Daisuke Obinata2

  • 1Department of Systems Aging Science and Medicine, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan.

Cancer Science
|August 28, 2019
PubMed

Insights

Octamer transcription factor 1 (OCT1) regulates prostate cancer growth. OCT1 knockdown and its target genes, DLGAP5 and NUF2, suppress castration-resistant prostate cancer progression and migration.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Octamer transcription factor 1 (OCT1) interacts with the androgen receptor (AR) and influences gene expression in prostate cancer.
  • The specific role of OCT1 in castration-resistant prostate cancer (CRPC) remains largely undefined.

Purpose of the Study:

  • To investigate the function of OCT1 in AR-positive CRPC using 22Rv1 cells.
  • To identify AR and OCT1 target genes involved in CRPC progression.

Main Methods:

  • Utilized 22Rv1 cells as an AR-positive CRPC model.
  • Performed OCT1 knockdown experiments.
  • Employed microarray analysis to identify target genes.
  • Conducted knockdown of identified target genes (DLGAP5, NUF2).
  • Performed immunohistochemical analysis on prostate cancer specimens.

Main Results:

  • OCT1 knockdown inhibited proliferation and migration in 22Rv1 cells.
  • Identified four AR and OCT1 target genes: DLGAP5, KIF15, NCAPG, and NUF2.
  • Knockdown of DLGAP5 and NUF2 suppressed 22Rv1 cell growth and migration.
  • Positive DLGAP5 expression correlated with poorer cancer-specific survival rates.
  • DLGAP5 expression was elevated in CRPC tissues.

Conclusions:

  • OCT1 plays a significant role in CRPC progression.
  • The AR/OCT1 complex regulates key genes (DLGAP5, KIF15, NCAPG, NUF2) implicated in CRPC.
  • DLGAP5 is a potential biomarker for poor prognosis in prostate cancer and is upregulated in CRPC.

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