@article{c4de3b7548da4ba296d8b7a38bdcb6aa,
title = "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{\textquoteright} 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.",
keywords = "Androgen receptor, NONO, PSF, Prostate cancer, RNA-binding protein",
author = "Takayama, {Ken ichi} and Takashi Suzuki and Tetsuya Fujimura and Yuta Yamada and Satoru Takahashi and Yukio Homma and Yutaka Suzuki and Satoshi Inoue",
note = "Funding Information: ACKNOWLEDGMENTS. We thank RIKEN for sequencing our samples. We are grateful to E. Sakamoto, N. Sasaki, and T. Oishi for technical assistance. This work was supported by grants of the Cell Innovation Program, the P-DIRECT, and the P-CREATE from Ministry of Education, Culture, Sports, Science and Technology, Japan (to S.I.); Japan Society for the Promotion of Science, Japan Grant 15K15581 (to K.T.) and Grant 15K15353 (to S.I.); a grant of the Program for Promotion of Fundamental Studies in Health Sciences from the National Institute of Biomedical Innovation, Japan (to S.I.); Grants-in-Aid from the Ministry of Health, Labor and Welfare, Japan (to S.I.); and grants from the Terumo Foundation for Life Sciences and Arts (to K.T.), the Princess Takamatsu Cancer Research Fund (to K.T.), and Uehara Memorial Foundation, Japan [201520122j (to S.I.)]. Publisher Copyright: {\textcopyright} 2017, National Academy of Sciences. All rights reserved.",
year = "2017",
month = sep,
day = "26",
doi = "10.1073/pnas.1706076114",
language = "English",
volume = "114",
pages = "10461--10466",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
publisher = "National Academy of Sciences",
number = "39",
}
