Dysregulation of spliceosome gene expression in advanced prostate cancer by RNA-binding protein PSF

Ken ichi Takayama, Takashi Suzuki, Tetsuya Fujimura, Yuta Yamada, Satoru Takahashi, Yukio Homma, Yutaka Suzuki, Satoshi Inoue

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Developing therapeutic approaches are necessary for treating hormone-refractory prostate cancer. Activation of androgen receptor (AR) and its variants’ expression along with the downstream signals are mostly important for disease progression. However, the mechanism for marked increases of AR signals and its expression is still unclear. Here, we revealed that various spliceosome genes are aberrantly induced by RNA-binding protein PSF, leading to enhancement of the splicing activities for AR expression. Our high-speed sequence analyses identified global PSF-binding transcripts. PSF was shown to stabilize and activate key long noncoding RNAs and AR-regulated gene expressions in prostate cancer cells. Interestingly, mRNAs of spliceosome-related genes are putative primary targets of PSF. Their gene expressions are up-regulated by PSF in hormone-refractory prostate cancer. Moreover, PSF coordinated these spliceosome proteins to form a complex to promote AR splicing and expression. Thus, targeting PSF and its related pathways implicates the therapeutic possibility for hormone-refractory prostate cancer.

Original languageEnglish
Pages (from-to)10461-10466
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume114
Issue number39
DOIs
Publication statusPublished - 2017 Sep 26

Keywords

  • Androgen receptor
  • NONO
  • PSF
  • Prostate cancer
  • RNA-binding protein

ASJC Scopus subject areas

  • General

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