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Splicing Factors Have an Essential Role in Prostate Cancer Progression and Androgen Receptor Signaling

1
Department of Functional Biogerontology, Tokyo Metropolitan Institute of Gerontology, 35-2 Sakae-cho, Itabashi-ku, Tokyo 173-0015, Japan
2
Department of Geriatric Medicine, Graduate School of Medicine, the University of Tokyo, 7-3-1 Hongo, Bunkyo-ku 113-0033, Japan
Biomolecules 2019, 9(4), 131; https://doi.org/10.3390/biom9040131
Received: 16 February 2019 / Revised: 16 March 2019 / Accepted: 26 March 2019 / Published: 1 April 2019
(This article belongs to the Special Issue Hormone Receptors in Cancer)
Although inhibition of the androgen–androgen receptor (AR) axis effectively represses the growth of prostate cancer, most of all cases eventually become castration-resistant prostate cancers (CRPCs). Enhancement of the expression of AR and its variants along with the downstream signals is important for disease progression. AR-V7, a constitutive active form of AR, is generated as a result of RNA splicing. RNA splicing creates multiple transcript variants from one pre-messenger RNA (mRNA) by removing introns/exons to allow mRNA translation. The molecular mechanisms leading to marked increases of AR and generation of AR-V7 have been unclear. However, recent papers highlighted the roles of RNA splicing factors which promote AR expression and production of variants. Notably, a broad range of splicing components were aberrantly regulated in CRPC tissues. Interestingly, expression of various spliceosome genes is enhanced by RNA-binding protein splicing factor proline- and glutamine-rich (PSF/SFPQ), leading to changes in the expression of AR transcript variants. Moreover, inhibition of several splicing factors repressed tumor growth in vivo. Altered expression of splicing factors is correlated to biochemical recurrence in prostate cancer patients. Thus, these findings suggest that splicing factors would be a potential therapeutic target. This review focuses on the emerging roles of splicing factors in prostate cancer progression and AR signaling. View Full-Text
Keywords: prostate cancer; androgen receptor; splicing factor; PSF; NONO prostate cancer; androgen receptor; splicing factor; PSF; NONO
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Takayama, K.-I. Splicing Factors Have an Essential Role in Prostate Cancer Progression and Androgen Receptor Signaling. Biomolecules 2019, 9, 131.

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