Circular RNAs add diversity to androgen receptor isoform repertoire in castration-resistant prostate cancer
作者： Subing Cao , Tianfang Ma , Nathan Ungerleider , Claire Roberts , Margaret Kobelski
DOI: 10.1038/S41388-019-0947-7
关键词:
摘要: Deregulated expression of circular RNAs (circRNAs) is associated with various human diseases, including many types cancer. Despite their growing links to cancer, there has been limited characterization circRNAs in metastatic castration-resistant prostate the major cause cancer mortality. Here, through analysis an exome-capture RNA-seq dataset from 47 samples and ribodepletion RNase R RNA-sequencing patient-derived xenografts (PDXs) cell models, we identified 13 generated key driver gene-androgen receptor (AR). We validated characterized top four most abundant, clinically relevant AR circRNAs. Expression these was upregulated during progression PDXs. The upregulation not due global increase circRNA formation tumors. Instead, levels correlated strongly that linear transcripts (both variants) clinical PDXs, indicating a transcriptional mechanism regulation. In cultured cells, androgen suppressed transcripts, suppression attenuated by antiandrogen. Using nuclear/cytoplasmic fractionation RNA in-situ hybridization assays, demonstrated predominant cytoplasmic localization circRNAs, likely functions. Overall, this first comprehensive arising gene. With greater resistance exoribonuclease compared detectability patient plasma, may serve as surrogate circulating markers for AR/AR-variant progression.
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