The Androgen Receptor as a Therapeutic Target for Castration-Resistant Prostate Cancer

2014 ◽  
pp. 77-94
Author(s):  
Jarett L. Feldman ◽  
Dana Rathkopf ◽  
Michael J. Morris
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Therapeutic Target ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant

scholarly journals Identification of Androgen Receptor Variant 7-related RNAs Affecting Abiraterone Efficacy in Castration-resistant Prostate Cancer Treatment by RNA-sequencing

2020 ◽  
Author(s):  
Shuo Wang ◽  
Yudong Cao ◽  
Xingxing Tang ◽  
Yong Yang ◽  
Peng Du
Keyword(s):  
Prostate Cancer ◽  
Survival Analysis ◽  
Androgen Receptor ◽  
Rna Sequencing ◽  
Therapeutic Target ◽  
Castration Resistant Prostate Cancer ◽  
Ppi Network ◽  
Castration Resistant ◽  
Erbb Signaling ◽  
Erbb Signaling Pathway

Abstract Background: This study aimed to identify androgen receptor variant 7 (AR-V7)-related RNAs affecting Abiraterone treatment of castration-resistant prostate cancer (CRPC) using RNA-sequencing. Methods: To identify AR-V7-related RNAs affecting Abiraterone treatment of CRPC, a series of in vitro experiments were employed, including cell proliferation assay, cell apoptosis assay, Western blot analysis, and Real-time quantitative reverse transcription PCR (qRT-PCR). After RNA-sequencing, the differentially expressed (DE) mRNAs and DE long non-coding RNAs (lncRNAs) were screened and the lncRNA-mRNA pairs were identified. In addition, enrichment and Protein-protein interaction (PPI) network analyses were performed. Finally, the mRNA-miRNA-lncRNA competing endogenous RNAs (ceRNA) network was built, along with survival analysis. Results: A total of 1,387 AR-V7-related RNAs affecting Abiraterone treatment of CRPC were identified. The enrichment analysis showed that the target genes of DEmRNAs and DElncRNAs were primarily involved in cancer-related pathways, including the ErbB signaling pathway, pathways in cancer, and basal cell carcinoma. In addition, notch receptor 1 (NOTCH1), ionotropic NMDA glutamate receptor type subunit 1 (GRIN1), U-box containing protein 1 (STUB1), and mitogen-activated protein kinase 7 (MAP2K7) with high degrees in the PPI network. Moreover, MAP2K7 was regulated by hsa-miR-6825-5p, which in turn was regulated by MAFG-AS1 lncRNA in the ceRNA network. The survival analysis revealed that a total of four lncRNAs, including MAFG-AS1, and 17 mRNAs, including high muscle blind-like splicing regulator 2 (MBNL2), were associated with disease-free survival (RFS). Among them, only MBNL2 overexpression correlated with good survival outcome. The NOTCH1, GRIN1, STUB1, MBNL2, and ErbB signaling pathways are likely related to the efficacy of Abiraterone in CRPC treatment. Moreover, the MAFG-AS1-hsa-miR-6825-5p-MAP2K7 axis could be a therapeutic target for Abiraterone in CRPC treatment.Conclusions: NOTCH1, GRIN1, STUB1, MBNL2, and the ErbB signaling pathway may relate to the progression of CRPC. MAFG-AS1-hsa-miR-6825-5p-MAP2K7 axis might be a potential therapeutic target for Abiraterone in CRPC.

scholarly journals Circular RNA cir-ITCH Is a Potential Therapeutic Target for the Treatment of Castration-Resistant Prostate Cancer

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Shoubin Li ◽  
Chunhong Yu ◽  
Yunxia Zhang ◽  
Junjiang Liu ◽  
Yi Jia ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Cell Lines ◽  
Therapeutic Target ◽  
Critical Role ◽  
Circular Rna ◽  
Migration And Invasion ◽  
Castration Resistant Prostate Cancer ◽  
Normal Prostate ◽  
Castration Resistant

cir-ITCH, a well-known tumor-suppressive circular RNA, plays a critical role in different cancers. However, its expression and functional role in prostate cancer (PCa) are unclear. Herein, we explored the potential mechanism and tumor-inhibiting role of cir-ITCH in PCa. Using reverse transcriptase polymerase chain reaction assay, we analyzed the expression of cir-ITCH in PCa and paired adjacent nontumor tissue samples resected during surgical operation, as well as in two cell lines of human PCa (LNCaP and PC-3) and the immortalized normal prostate epithelial cell line (RWPE-1). Cell viability and migration of PCa cell lines were evaluated using CCK-8 and wound-healing assays. Expression of key proteins of the Wnt/β-catenin and PI3K/AKT/mTOR pathways was detected using western blotting. We found that cir-ITCH expression was typically downregulated in the tissues and cell lines of PCa compared to that in the peritumoral tissue and in RWPE-1 cells, respectively. The results showed that cir-ITCH overexpression significantly inhibits the proliferation, migration, and invasion of human PCa cells and that reciprocal inhibition of expression occurred between cir-ITCH and miR-17. Proteins in the Wnt/β-catenin and PI3K/AKT/mTOR pathways were downregulated by overexpression of cir-ITCH both in androgen receptor-positive LNCaP cells and androgen receptor-negative PC-3 cells. Taken together, these data demonstrated that cir-ITCH plays a tumor-suppressive role in human PCa cells, partly through the Wnt/β-catenin and PI3K/AKT/mTOR pathways. Thus, cir-ITCH may serve as a novel therapeutic target for the treatment of PCa, especially castration-resistant prostate cancer.

scholarly journals Interplay Between SOX9, Wnt/β-Catenin and Androgen Receptor Signaling in Castration-Resistant Prostate Cancer

2019 ◽  
Vol 20 (9) ◽  
pp. 2066 ◽  
Author(s):  
Namrata Khurana ◽  
Suresh C. Sikka
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Signaling Pathways ◽  
Critical Role ◽  
Castration Resistant Prostate Cancer ◽  
Form Complex ◽  
Androgen Receptor Signaling ◽  
Castration Resistant ◽  
Signaling Axis

Androgen receptor (AR) signaling plays a key role not only in the initiation of prostate cancer (PCa) but also in its transition to aggressive and invasive castration-resistant prostate cancer (CRPC). However, the crosstalk of AR with other signaling pathways contributes significantly to the emergence and growth of CRPC. Wnt/β-catenin signaling facilitates ductal morphogenesis in fetal prostate and its anomalous expression has been linked with PCa. β-catenin has also been reported to form complex with AR and thus augment AR signaling in PCa. The transcription factor SOX9 has been shown to be the driving force of aggressive and invasive PCa cells and regulate AR expression in PCa cells. Furthermore, SOX9 has also been shown to propel PCa by the reactivation of Wnt/β-catenin signaling. In this review, we discuss the critical role of SOX9/AR/Wnt/β-catenin signaling axis in the development and progression of CRPC. The phytochemicals like sulforaphane and curcumin that can concurrently target SOX9, AR and Wnt/β-catenin signaling pathways in PCa may thus be beneficial in the chemoprevention of PCa.

scholarly journals Androgen receptor mutations in patients with castration-resistant prostate cancer treated with apalutamide

2017 ◽  
Vol 28 (9) ◽  
pp. 2264-2271 ◽  
Author(s):  
D.E. Rathkopf ◽  
M.R. Smith ◽  
C.J. Ryan ◽  
W.R. Berry ◽  
N.D. Shore ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant
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