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

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.

SUBMITTER: Takayama KI 

PROVIDER: S-EPMC5625911 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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

Takayama Ken-Ichi KI   Suzuki Takashi T   Fujimura Tetsuya T   Yamada Yuta Y   Takahashi Satoru S   Homma Yukio Y   Suzuki Yutaka Y   Inoue Satoshi S  

Proceedings of the National Academy of Sciences of the United States of America 20170911 39

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 expre  ...[more]

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