Emerging proteins involved in castration‑resistant prostate cancer via the AR‑dependent and AR‑independent pathways (Review)

Feng, Kangle; Liu, Chunhua; Wang, Weixi; Kong, Piaoping; Tao, Zhihua; Liu, Weiwei

doi:10.3892/ijo.2023.5575

“…These hormones exert their effects by binding to the androgen receptor (AR), which then activates a cascade of genetic expressions that promote cellular growth and survival [9]. In the context of prostate cancer, the AR pathway is a critical driver of tumor growth and progression, making it a primary target for therapeutic intervention [10,11]. androgen deprivation therapy (ADT), which inhibit the action of testosterone or the AR itself, have been standard treatments and provide signi cant bene ts in many cases [12][13][14].…”

Section: Introductionmentioning

confidence: 99%

Insights into Immune Microenvironment and Therapeutic Targeting in Androgen-Associated Prostate Cancer Subtypes

Huang,

Xie,

Jiang

et al. 2024

Preprint

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Prostate cancer, one of the most prevalent malignancies among men worldwide, is intricately linked with androgen signaling, a key driver of its pathogenesis and progression. Understanding the diverse expression patterns of androgen-responsive genes holds paramount importance in unraveling the biological intricacies of this disease and prognosticating patient outcomes. In this study, utilizing consensus clustering analysis based on the expression profiles of androgen-responsive genes, prostate cancer patients from the TCGA database were stratified into two distinct subtypes, denoted as C1 and C2. Notably, the C1 subtype demonstrates a significant upregulation of certain genes, such as CGA and HSD17B12, along with a shorter progression-free survival duration, indicating a potentially unfavorable prognosis. Further analyses elucidated the immune infiltration disparities, mutation landscapes, and gene functional pathways characteristic of each subtype. Through integrated bioinformatics approaches and machine learning techniques, key genes such as BIRC5, CENPA, and MMP11 were identified as potential therapeutic targets, providing novel insights into tailored treatment strategies. Additionally, single-cell transcriptome analysis shed light on the heterogeneous expression patterns of these genes across different cell types within the tumor microenvironment. Furthermore, virtual screening identified candidate drugs targeting the BIRC5 receptor, offering promising avenues for drug development. Collectively, these findings deepen our understanding of prostate cancer biology, paving the way for personalized therapeutic interventions and advancing the quest for more effective treatments in prostate cancer management.

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AR expression-independent XRCC3 mediates DNA damage-induced p53/Bax signaling pathway activation against prostate cancer

Xie,

Dan,

Cen

et al. 2024

J Cancer Res Clin Oncol

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Background Androgen deprivation therapy (ADT) resistance is closely associated with altered AR status. Aberrant AR expression is critical for the induction of ADT resistance, necessitating the identification of an anti-PCa target independent of AR expression. Methods Transcriptomic data and clinical information of PRAD were obtained from TCGA database. Genes with PCa-related and AR expression-independent were screened by bioinformatics, and characterized by PPI and GO functional enrichment analyses. Candidate genes were locked by co-expression correlation and disease-free survival (DFS) analyses. A prognostic gene set was established using LASSO Cox regression algorithm. Cox proportional risk regression was performed to identify a key prognostic gene. Expression of the target protein in PCa tissues was verified by The Human Protein Atlas database. In vitro validation of cellular function and molecular mechanism by knockdown and overexpression of the target gene. Results Two AR expression-independent genes (SLC43A1 and XRCC3) were available for the optimal prognostic model. This gene set effectively predicted PRAD patients’ DFS at 1-, 3- and 5-year, where XRCC3 and tumor (T) stage were independent risk factors. XRCC3 was higher expressed in PRAD patients with T3-T4 stages and accompanied by poorer DFS. IHC staining also validated its higher expression in high-risk PCa tissues. In vitro experiments demonstrated that silencing XRCC3 significantly inhibited 22Rv1 and DU145 cell proliferation, migration and invasion, while promoted apoptosis. Further, silencing XRCC3 promoted DNA damage-induced p53/Bax signaling pathway activation, which was absent with overexpression. Conclusion Silencing XRCC3 exerts anti-PCa effects by promoting DNA damage-induced p53/Bax signaling pathway activation in an AR expression-independent manner. Supplementary Information The online version contains supplementary material available at 10.1007/s00432-024-05989-8.

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Insights into immune microenvironment and therapeutic targeting in androgen-associated prostate cancer subtypes

Huang,

Xie,

Jiang

et al. 2024

Sci Rep

0

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Prostate cancer, one of the most prevalent malignancies among men worldwide, is intricately linked with androgen signaling, a key driver of its pathogenesis and progression. Understanding the diverse expression patterns of androgen-responsive genes holds paramount importance in unraveling the biological intricacies of this disease and prognosticating patient outcomes. In this study, utilizing consensus clustering analysis based on the expression profiles of androgen-responsive genes, prostate cancer patients from the TCGA database were stratified into two distinct subtypes, denoted as C1 and C2. Notably, the C1 subtype demonstrates a significant upregulation of certain genes, such as CGA and HSD17B12, along with a shorter progression-free survival duration, indicating a potentially unfavorable prognosis. Further analyses elucidated the immune infiltration disparities, mutation landscapes, and gene functional pathways characteristic of each subtype. Through integrated bioinformatics approaches and machine learning techniques, key genes such as BIRC5, CENPA, and MMP11 were identified as potential therapeutic targets, providing novel insights into tailored treatment strategies. Additionally, single-cell transcriptome analysis shed light on the heterogeneous expression patterns of these genes across different cell types within the tumor microenvironment. Furthermore, virtual screening identified candidate drugs targeting the BIRC5 receptor, offering promising avenues for drug development. Collectively, these findings deepen our understanding of prostate cancer biology, paving the way for personalized therapeutic interventions and advancing the quest for more effective treatments in prostate cancer management.

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Emerging proteins involved in castration‑resistant prostate cancer via the AR‑dependent and AR‑independent pathways (Review)

Cited by 4 publications

References 172 publications

Insights into Immune Microenvironment and Therapeutic Targeting in Androgen-Associated Prostate Cancer Subtypes

Insights into Immune Microenvironment and Therapeutic Targeting in Androgen-Associated Prostate Cancer Subtypes

AR expression-independent XRCC3 mediates DNA damage-induced p53/Bax signaling pathway activation against prostate cancer

Insights into immune microenvironment and therapeutic targeting in androgen-associated prostate cancer subtypes

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