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

Takayama Ken-ichi; Suzuki Takashi; Fujimura TetsuyaYamada YutaTakahashi SatoruHomma YukioSuzuki YutakaInoue Satoshi

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

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

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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.

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《Proceedings of the National Academy of Sciences of the United States of America.》 |2017年第39期|10461-10466|共6页
作者
Takayama Ken-ichi; Suzuki Takashi; Fujimura TetsuyaYamada YutaTakahashi SatoruHomma YukioSuzuki YutakaInoue Satoshi;
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作者单位

Tokyo Metropolitan Inst Gerontol, Dept Funct Biogerontol, Tokyo 1730015, Japan;

Tohoku Univ, Grad Sch Med, Dept Pathol & Histotechnol, Sendai, Miyagi 9808575, Japan;

Univ Tokyo, Grad Sch Med, Dept Urol, Tokyo 1138655, JapanNihon Univ, Sch Med, Dept Urol, Tokyo 1730032, JapanUniv Tokyo, Grad Sch Frontier Sci, Dept Med Genome Sci, Chiba 2778652, Japan;

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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种英语
中图分类自然科学总论;
关键词
androgen receptor; RNA-binding protein; PSF; NONO; prostate cancer;

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

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