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

被引：89

作者：

Takayama, Ken-ichi ^{[1
]}

Suzuki, Takashi ^{[2
]}

Fujimura, Tetsuya ^{[3
]}

Yamada, Yuta ^{[3
]}

Takahashi, Satoru ^{[4
]}

Homma, Yukio ^{[3
]}

Suzuki, Yutaka ^{[5
]}

Inoue, Satoshi ^{[1
,6
]}

机构：

[1] Tokyo Metropolitan Inst Gerontol, Dept Funct Biogerontol, Tokyo 1730015, Japan

[2] Tohoku Univ, Grad Sch Med, Dept Pathol & Histotechnol, Sendai, Miyagi 9808575, Japan

[3] Univ Tokyo, Grad Sch Med, Dept Urol, Tokyo 1138655, Japan

[4] Nihon Univ, Sch Med, Dept Urol, Tokyo 1730032, Japan

[5] Univ Tokyo, Grad Sch Frontier Sci, Dept Med Genome Sci, Chiba 2778652, Japan

[6] Saitama Med Univ, Res Ctr Genom Med, Div Gene Regulat & Signal Transduct, Saitama 3501241, Japan

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2017年 / 114卷 / 39期

基金：

日本学术振兴会;

关键词：

androgen receptor; RNA-binding protein; PSF; NONO; prostate cancer; NONCODING RNA; SPLICING FACTOR; RESISTANCE; SFPQ; TRANSCRIPTION; RECOGNITION; PROGRESSION; METABOLISM; MECHANISMS; MUTATIONS;

D O I：

10.1073/pnas.1706076114

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 PSFbinding 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.

引用

页码：10461 / 10466

页数：6

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