scholarly journals RNA‐binding protein Musashi2 stabilizing androgen receptor drives prostate cancer progression

2020 ◽  
Vol 111 (2) ◽  
pp. 369-382
Author(s):  
Jing Zhao ◽  
Yu Zhang ◽  
Xi‐sheng Liu ◽  
Fang‐ming Zhu ◽  
Feng Xie ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Cancer Progression ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Prostate Cancer Progression

INVESTIGATION OF THE ROLE OF GRSF-1 RNA BINDING PROTEIN IN PROSTATE CANCER PROGRESSION

1999 ◽  
pp. 61
Author(s):  
Michael E. Chen ◽  
Gail C. Fraizer ◽  
Tasneem Ahmed ◽  
Bei Zheng ◽  
Jeffrey Wilusz ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Progression ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Prostate Cancer Progression

The RNA-binding protein FXR1 modulates prostate cancer progression by regulating FBXO4

2019 ◽  
Vol 19 (3) ◽  
pp. 487-496 ◽  
Author(s):  
Hongwen Cao ◽  
Renjie Gao ◽  
Chao Yu ◽  
Lei Chen ◽  
Yigeng Feng
Keyword(s):  
Prostate Cancer ◽  
Cancer Progression ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Prostate Cancer Progression

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

Biomolecules ◽  
2019 ◽  
Vol 9 (4) ◽  
pp. 131 ◽  
Author(s):  
Ken-ichi Takayama
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Cancer Progression ◽  
Rna Splicing ◽  
Rna Binding ◽  
Mrna Translation ◽  
Splicing Factors ◽  
Prostate Cancer Progression ◽  
Altered Expression ◽  
Transcript Variants

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.

scholarly journals RNA-binding protein DDX3 mediates posttranscriptional regulation of androgen receptor: A mechanism of castration resistance

2020 ◽  
Vol 117 (45) ◽  
pp. 28092-28101 ◽  
Author(s):  
Jordan E. Vellky ◽  
Sean T. McSweeney ◽  
Emily A. Ricke ◽  
William A. Ricke
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Protein Expression ◽  
Messenger Rna ◽  
Posttranscriptional Regulation ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Protein Translation

Prostate cancer (CaP) driven by androgen receptor (AR) is treated with androgen deprivation; however, therapy failure results in lethal castration-resistant prostate cancer (CRPC). AR-low/negative (ARL/−) CRPC subtypes have recently been characterized and cannot be targeted by hormonal therapies, resulting in poor prognosis. RNA-binding protein (RBP)/helicase DDX3 (DEAD-box helicase 3 X-linked) is a key component of stress granules (SG) and is postulated to affect protein translation. Here, we investigated DDX3-mediated posttranscriptional regulation of AR mRNA (messenger RNA) in CRPC. Using patient samples and preclinical models, we objectively quantified DDX3 and AR expression in ARL/− CRPC. We utilized CRPC models to identify DDX3:AR mRNA complexes by RNA immunoprecipitation, assess the effects of DDX3 gain/loss-of-function on AR expression and signaling, and address clinical implications of targeting DDX3 by assessing sensitivity to AR-signaling inhibitors (ARSI) in CRPC xenografts in vivo. ARL/− CRPC expressed abundant AR mRNA despite diminished levels of AR protein. DDX3 protein was highly expressed in ARL/− CRPC, where it bound to AR mRNA. Consistent with a repressive regulatory role, DDX3 localized to cytoplasmic puncta with SG marker PABP1 in CRPC. While induction of DDX3-nucleated SGs resulted in decreased AR protein expression, inhibiting DDX3 was sufficient to restore 1) AR protein expression, 2) AR signaling, and 3) sensitivity to ARSI in vitro and in vivo. Our findings implicate the RBP protein DDX3 as a mechanism of posttranscriptional regulation for AR in CRPC. Clinically, DDX3 may be targetable for sensitizing ARL/− CRPC to AR-directed therapies.

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