The linear mRNAs transcribed under alternative RNA splicing and overexpression/amplification of the
androgen receptor (AR) gene are poor prognostic
biomarkers of castrate-resistant
prostate cancer (PCa). Whether the AR gene also transcribes non-coding
circular RNAs that are associated with PCa development and
tumor progression remains unclear. Here, we identified and characterized an AR
circular RNA, called circAR3, that is widely expressed in PCa cell models and prostate
tumors. circAR3 can be secreted into
culture media of PCa cell lines and is detectable in the serum from mice bearing PCa xenografts. In PCa patient tissues, circAR3 is highly expressed in benign prostate and
hormone naive PCa but downregulated when
tumors were treated with neoadjuvant
hormone therapy and further reduced when
tumors progressed to the castrate-resistant stage. However, circAR3 levels in plasma are extremely low in patients with benign prostate, are upregulated in PCa patients with high Gleason scores and
lymph node metastasis, and become undetectable in men after radical
prostatectomy. circAR3 does not affect AR signaling, PCa cell proliferation, and invasion rates. Our results demonstrated that the origin of the detectable plasma circAR3 is from the prostate/PCa. Plasma circAR3 may be developed to be a PCa biomarker to monitor PCa development and
tumor progression.