PacRim7 7th PacRim Meeting Poster Presentations (1) (52 abstracts)
Circular RNAs add further diversity to AR isoform repertoire
Subing Cao 1 , Tianfang Ma 1 , Nathan Ungerleider 2 , Claire Roberts 2 , Lianjin Jin 1 , Monica Concha 2 , Xia Wang 2 , Melody Baddoo 2 , Ladan Fazli 3 , Eva Corey 4 , Oliver Sartor 5 , Xuesen Dong 3 , Erik Flemington 2,* & Yan Dong 1
1Department of Structural and Cellular Biology, Tulane University, New Orleans, Louisiana, USA; 2Department of Pathology, Tulane University, New Orleans, Louisiana, USA; 3Department of Urologic Sciences, Vancouver Prostate Centre, University of British Columbia, Vancouver, British Columbia, Canada; 4Department of Urology, University of Washington, Seattle, Washington, USA; 5Department of Medicine, Tulane University, New Orleans, Louisiana, USA. *Presenter
Circular RNAs (circRNAs) are a newly appreciated class of regulatory RNA species that play vital roles in various cell signaling and metabolic processes. Deregulated expression of circRNAs has been found to be associated with various human diseases including many types of cancer. Despite their growing links to cancer, there has been limited characterization of circRNAs in metastatic castration-resistant prostate cancer, the major cause of prostate cancer mortality. Here, initiated with a global analysis using a publically available exome capture RNA-seq dataset from 47 metastatic castration-resistant prostate cancer samples, we identified circRNAs generated from the key prostate cancer driver gene-androgen receptor (AR). We validated and characterized the top four most abundant AR circRNAs using RNase R RNA-seq. Expression of these AR circRNAs as upregulated in castration-resistant compared to hormone naïve patient-derived xenografts and was further increased in enzalutamide-resistant patient-derived xenografts. The upregulation of these AR circRNAs was not due to global increase of circRNA formation in these tumors. Instead, the levels of AR circRNAs correlated strongly with that of the linear AR transcripts (both full-length AR and AR splice variants) in clinical samples and patient-derived xenografts. In cultured cells, androgen supplementation led to a significant downregulation of these AR circRNAs as well as the linear AR transcripts, and the downregulation was attenuated by enzalutamide treatment. Using nuclear/cytoplasmic fractionation and the Basescope RNA in-situ hybridization assay, we demonstrated predominant cytoplasmic localization of these AR circRNAs, indicating likely cytoplasmic functions. CircRNAs have previously been shown to be secreted into the circulation and readily detectable in the plasma. With higher exoribonuclease resistance and RNA stability compared to the linear AR transcripts, these AR circRNAs may serve as a new species of circulating biomarker for metastatic castration-resistant prostate cancer patients.
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Oncology Abstracts
ISSN 2631-4657 (online)
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