ArticleJournal of translational medicine2025
A novel peptide encoded by circSRCAP confers resistance to enzalutamide by inhibiting the ubiquitin-dependent degradation of AR-V7 in castration-resistant prostate cancer.
Article in Journal of translational medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
6 citing papers in PubMed.
- Noncoding RNA encoded peptides in tumors from discovery to mechanism and clinical translation.iScience · 2026Review
- KDM5B-driven glucose metabolic reprogramming promotes enzalutamide resistance in prostate cancer via the lactate/hnRNPA1 lactylation/AR-V7 axis.Molecular cancer · 2026Article
- Alterations in AR-FOXA1 signaling in prostate cancer progression and therapeutic resistance.Journal of the National Cancer Center · 2026Review
- Inhibition of the RORC/GPX4 mediated ferroptosis regulatory axis suppresses tumor growth and alleviates enzalutamide resistance in prostate cancer.Cellular & molecular biology letters · 2026Article
- Research progress on circular RNA in the regulation of drug resistance in genitourinary cancers.Cellular and molecular life sciences : CMLS · 2025Review
- Small open reading frame-encoded microproteins in cancer: identification, biological functions and clinical significance.Molecular cancer · 2025Review
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
backgroundThe sustained activation of androgen receptor splice variant-7 (AR-V7) is a key factor in the resistance of castration-resistant prostate cancer (CRPC) to second-generation anti-androgens such as enzalutamide (ENZ). The AR/AR-V7 protein is regulated by the E3 ubiquitin ligase STUB1 and a complex involving HSP70, but the precise mechanism remains unclear.
methodsHigh-throughput RNA sequencing was used to identify differentially expressed circular RNAs (circRNAs) in ENZ-resistant and control CRPC cells. The coding potential of circSRCAP was confirmed by polysome profiling and LC-MS. The function of circSRCAP was validated in vitro and in vivo using gain- and loss-of-function assays. Mechanistic insights were obtained through immunoprecipitation analyses.
resultsA novel ENZ-resistant circRNA, circSRCAP, was identified and shown to be upregulated in ENZ-resistant C4-2B (ENZR-C4-2B) cells, correlating with increased AR-V7 protein levels. circSRCAP is generated via splicing by eIF4A3, forming a loop structure and is exported from the nucleus by the RNA helicase DDX39A. Mechanistically, circSRCAP encodes a 75-amino acid peptide (circSRCAP-75aa) that inhibits the ubiquitination of AR/AR-V7's co-chaperone protein HSP70 by disrupting the interaction with the E3 ligase STUB1. This process results in the upregulation of AR-V7 expression and promotes ENZ resistance in CRPC cells. Xenograft tumor models further confirmed the role of circSRCAP in CRPC progression and its potential as a therapeutic target for ENZ-resistant CRPC.
conclusionscircSRCAP provides an epigenetic mechanism influencing AR-V7 stability and offers a promising therapeutic target for treating ENZ-resistant CRPC.
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