The RNA helicase DDX39B and its paralog DDX39A regulate androgen receptor splice variant AR-V7 generation

Nakata, Daisuke; Nakao, Shigetomi; Nakayama, Keizo; Araki, Shinsuke; Nakayama, Yusuke; Aparicio, Samuel; Hara, Takahito; Nakanishi, Atsushi

doi:10.1016/j.bbrc.2016.12.153

Cited by 52 publications

(39 citation statements)

References 33 publications

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“…As a mechanism of splicing alterations, AR variants are induced via splicing modulation involving various molecules, including U2AF65, ASF/SF2, hnRNPA1, Sam68, Lin28, DDX39, and YB-1. 17,[26][27][28][29][30] In our study, induction of AR variants by TSC was accompanied by phosphorylation of Akt at Thr308, but no YB-1 phosphorylation, suggesting that an Akt-but not YB-1-mediated mechanism is responsible. Consistently, Akt inhibition by LY294002 suppressed expression of AR variants at the protein but not transcript level.…”

Section: Discussionmentioning

confidence: 45%

“…Presently, two mechanisms including genomic rearrangements in AR locus as well as splicing alterations are indicated. As a mechanism of splicing alterations, AR variants are induced via splicing modulation involving various molecules, including U2AF65, ASF/SF2, hnRNPA1, Sam68, Lin28, DDX39, and YB‐1 . In our study, induction of AR variants by TSC was accompanied by phosphorylation of Akt at Thr308, but no YB‐1 phosphorylation, suggesting that an Akt‐ but not YB‐1‐mediated mechanism is responsible.…”

Section: Discussionmentioning

confidence: 48%

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Cigarette smoking augments androgen receptor activity and promotes resistance to antiandrogen therapy

et al. 2019

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Background Cigarette smoking is associated with worse outcomes in prostate cancer, whose growth is dependent on androgen receptor (AR) signaling. We aimed to elucidate the biological effect of cigarette smoking on AR signaling and its clinical influence on oncological outcome. Methods Gene expression levels after exposure to tobacco smoke condensate (TSC) were evaluated by quantitative real‐time polymerase chain reaction and Western blot analysis in prostate cancer cells. Cellular sensitivities to enzalutamide and docetaxel after TSC exposure were evaluated using a prostate cancer cell proliferation assay. Prognosis was compared between current smokers and nonsmokers when treated with AR‐axis‐targeting (ARAT) agent enzalutamide and docetaxel. Results Expression of AR variants as well as prostate‐specific antigen was augmented after TSC exposure, which occurred after Akt phosphorylation. These inductions were suppressed by Akt inhibitor LY294002 as well as antioxidant N‐acetylcysteine. Consistently, TSC exposure augmented cellular resistance to enzalutamide. In clinical data, cigarette smoking was associated with worse progression‐free survival and cancer‐specific survival when patients with prostate cancer were treated with ARAT agents but not docetaxel. Conclusions It was suggested that cigarette smoking leads to detrimental oncological outcome when prostate cancer patients are treated with ARAT agents through induction of aberrant AR signaling. Accordingly, we recommend that patients with advanced prostate cancer should refrain from cigarette smoking.

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Section: Discussionmentioning

confidence: 45%

Section: Discussionmentioning

confidence: 48%

Cigarette smoking augments androgen receptor activity and promotes resistance to antiandrogen therapy

et al. 2019

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“…Thus far, it is unclear whether the modulation of IL-7 receptor expression is solely responsible for this genetic susceptibility. Since another study has shown that the androgen receptor is also targeted by DDX39B [75], it is plausible that DDX39B regulates the splicing of many other inflammatory mRNAs. Global identification of such targets will be necessary for the functional characterization of this RBP.…”

Section: Ddx39bmentioning

confidence: 99%

RNA binding proteins in the control of autoimmune diseases

Yoshinaga

Takeuchi

2019

Immunological Medicine

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Autoimmune disease is induced by the breakdown of immune tolerance to self-antigens. This is brought about by an imbalance between the activation and the repression of immune responses. Dysregulation of the immune response is driven by the excess of proinflammatory cytokines such as IL-6 and TNF, which play a central role in the pathogenesis of a set of autoimmune diseases. The expression of proinflammatory mediator genes is tightly controlled by post-transcriptional regulation, which is mediated by a set of immune-related RNA binding proteins, such as tristetraprolin, Roquin, and Regnase-1. These proteins coordinately control the stability of proinflammatory mRNAs to regulate aberrant immune reactions. In this review, we discuss the roles of RNA binding proteins which are associated with the immune regulation and autoimmune pathogenesis.

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“…Le premier consiste en un réarrangement au niveau du locus du gène du RA. Le deuxième repose sur une modification de l'expression de certains gènes du complexe protéique impliqué dans l'épissage, comme hnRNPA1 (heterogeneous nuclear ribonucleoprotein A1), DDX39A et DDX39B (DExD-Box helicase 39A et 39B)[27][28][29].…”

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Variants du récepteur des androgènes dans le cancer de la prostate

et al. 2017

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Prostate cancer is a public health concern as it currently represents the most frequent malignancy in men in Europe. Progression of this hormone-dependent cancer is driven by androgens. Thus, the most common treatment for patients with advanced prostate cancer consists in an androgen ablation by castration therapy. However, the majority of patients relapses and develops a castration-resistant prostate cancer. This failure of androgen deprivation is related to the emergence of mutant and splice variants of the androgen receptor. Indeed, androgen receptor variants are ligand-independent, constitutively active and thus able to induce resistance to castration. This review focuses on AR variants signaling pathways and their role in resistance to castration and prostate cancer progression.

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The RNA helicase DDX39B and its paralog DDX39A regulate androgen receptor splice variant AR-V7 generation

Cited by 52 publications

References 33 publications

Cigarette smoking augments androgen receptor activity and promotes resistance to antiandrogen therapy

Cigarette smoking augments androgen receptor activity and promotes resistance to antiandrogen therapy

RNA binding proteins in the control of autoimmune diseases

Variants du récepteur des androgènes dans le cancer de la prostate

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