Recent advances in prostate cancer (PCa) have led to the development of new treatments that target the androgen receptor (AR) pathway. However, some pts present with intrinsic resistance to treatment while others eventually develop acquired resistance. The mechanisms associated with the development of resistance have yet to be fully characterized. Non-coding RNAs (ncRNA) are RNA molecules, which are not translated into protein and include microRNAs (miRNA). Recently a novel type of ncRNA was identified and is termed circular RNA (circRNA). circRNA appear to play a crucial role in gene expression through the regulation of miRNAs. The aim of this study is to determine the role of circRNA in enzalutamide resistance and their interaction with miRNAs associated with PCa.
Total RNA was extracted from a panel of prostate cell lines, which included benign (n = 3), malignant (n = 5) and an isogenic model of enzalutamide resistance. circRNA profiling was performed using an Arraystar microarray platform. Differentially expressed circRNAs were ranked according to fold change between groups (FC >2; p-value
In total 9,757 circRNAs were classified as present across the panel of cell lines. Cell lines were stratified according to their AR status, malignancy status and resistance to enzalutamide. A number of differentially expressed circRNA were identified between the groups. The majority of circRNA were downregulated in enzalutamide resistant cells when compared with drug sensitive cells (280 upregulated v 550 downregulated). Predicted miRNA targets were determined for circRNAs with FC greater than 2. For each circRNA up and downregulated, 5 binding sites for their targeted miRNAs were identified allowing identification of circRNA/miIRNA interactions relevant to PCa.
circRNAs are differentially expressed based on AR and malignancy status, and enzalutamide sensitivity. Binding sites for miRNA associated with PCa can be identified on circRNA. This novel type of ncRNA may have a role as biomarkers in PCa and serve as predictive markers to enzalutamide therapy.
Clinical trial identification
Legal entity responsible for the study
Irish Cancer Society
All authors have declared no conflicts of interest.