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Updated: Jan 21, 2026

A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
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A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer

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Circular RNAs add diversity to androgen receptor isoform repertoire in castration-resistant prostate cancer

Subing Cao1, Tianfang Ma1, Nathan Ungerleider2

  • 1Department of Structural and Cellular Biology, Tulane University School of Medicine, Tulane Cancer Center, New Orleans, LA, USA.

Oncogene
|August 15, 2019
PubMed

Insights

Circular RNAs (circRNAs) from the androgen receptor (AR) gene are upregulated in metastatic castration-resistant prostate cancer. These AR circRNAs may serve as novel biomarkers for disease progression.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Circular RNAs (circRNAs) are increasingly linked to various cancers.
  • Metastatic castration-resistant prostate cancer (mCRPC) is a leading cause of cancer mortality.
  • Limited research exists on circRNAs in mCRPC, particularly those derived from the androgen receptor (AR) gene.

Purpose of the Study:

  • To identify and characterize circRNAs originating from the androgen receptor (AR) gene in metastatic castration-resistant prostate cancer.
  • To investigate the expression patterns and regulatory mechanisms of AR-derived circRNAs during castration resistance.
  • To explore the potential of AR circRNAs as diagnostic or prognostic biomarkers for mCRPC.

Main Methods:

  • Analysis of exome-capture RNA-sequencing data from 47 mCRPC samples.
  • RNA sequencing of patient-derived xenografts (PDXs) and cell models after ribodepletion and RNase R treatment.
  • Validation and characterization of top AR circRNAs using molecular assays.
  • Nuclear/cytoplasmic fractionation and RNA in-situ hybridization.

Main Results:

  • Thirteen circRNAs were identified from the AR gene in mCRPC samples.
  • The four most abundant AR circRNAs were validated and characterized.
  • AR circRNA expression was upregulated during castration-resistant progression in PDXs, correlating with linear AR transcript levels.
  • Androgen suppressed AR circRNA and linear AR transcript expression in cell models.
  • AR circRNAs were predominantly localized in the cytoplasm.
  • AR circRNAs were detected in patient plasma.

Conclusions:

  • This study provides the first comprehensive characterization of circRNAs derived from the AR gene.
  • AR circRNAs are transcriptionally regulated and their expression is linked to AR signaling.
  • Cytoplasmic localization suggests potential functional roles for AR circRNAs.
  • AR circRNAs show promise as stable circulating biomarkers for AR/AR-variant expression and mCRPC progression.

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