Abstract
Circular RNAs (circRNAs), a recently discovered non-coding RNA, have a number of functions including the regulation of miRNA expression. They have been detected in a number of malignancies including prostate cancer (PCa). The differential expression pattern of circRNAs associated with PCa and androgen receptor (AR) status was investigated in this study. circRNA profiling was performed using a high throughout microarray assay on a panel of prostate cell lines, which consisted of normal, benign, and malignant cells (n = 9). circRNAs were more commonly significantly up-regulated (p < 0.05) than downregulated in malignant cell lines (n = 3,409) vs. benign cell lines (n = 2,949). In a grouped analysis based on AR status, there were 2,127 down-regulated circRNAs in androgen independent cell lines compared to 2,236 in androgen dependent cell lines, thus identifying a potential circRNA signature reflective of androgen dependency. Through a bioinformatics approach, the parental genes associated with the top 10 differentially expressed circRNAs were identified such as hsa_circ_0064644, whose predicted parental gene target is RBMS3, and hsa_circ_0060539, whose predicted gene target is SDC4. Furthermore, we identified three circRNAs associated with the parental gene Caprin1 (hsa_circ_0021652, hsa_circ_0000288, and hsa_circ_0021647). Other studies have shown the importance of Caprin1 in PCa cell survival and drug resistance. Given the modified circRNA expression signatures identified here, these hypothesis generating results suggest that circRNAs may serve as potential putative diagnostic and predictive markers in PCa. However, further validation studies are required to assess the true potential of these markers in the clinical setting.
Highlights
Differential CircRNA Expression Signatures both to form exonic or intronic circRNAs (Jeck et al, 2013). circRNAs are covalently joined by their 3 - and 5 - ends, which are formed by back-splice events, presenting as closed continuous structures, making them highly stable and resistant to degradation (Salzman et al, 2012; Barrett et al, 2015). circRNAs have many postulated functions such as the regulation of miRNA function by controlling the expression of miRNAs through a “sponging effect,” this appears to apply to only a small number of circRNAs, such as ciRS-7 acting as a miR-7 sponge (Bahn et al, 2015)
It has been proposed that circRNAs may have a role in protein synthesis, with a number of circRNAs implicated in the translation of peptides, such as ZNF609 (Legnini et al, 2017). As research in this space increases, it is clear that the circRNA-miRNAmRNA network, plays an important role in both gene regulation and carcinogenesis (Su et al, 2019). circRNAs have been detected in prostate cancer, which make them an attractive research target (Greene et al, 2019).PCa growth and development is primarily dependent on the androgen receptor (AR), which is the target of therapeutic agents such as enzalutamide and abiraterone (Antonarakis et al, 2014)
We propose that circRNAs have the potential to serve as useful biomarkers to improve diagnostic screening for PCa and/or identify men who are at risk of developing castration-resistant disease
Summary
Non-coding RNAs (ncRNAs), which include microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) (Shih et al, 2015; Lin et al, 2017; Misawa et al, 2017), play an important role in gene regulation (Warner, 1999; Esteller, 2011; Jeck et al, 2013). circular RNAs (circRNAs), a recently discovered type of ncRNA, are generated from the backsplicing of exons, introns, or Differential CircRNA Expression Signatures both to form exonic or intronic circRNAs (Jeck et al, 2013). circRNAs are covalently joined by their 3 - and 5 - ends, which are formed by back-splice events, presenting as closed continuous structures, making them highly stable and resistant to degradation (Salzman et al, 2012; Barrett et al, 2015). circRNAs have many postulated functions such as the regulation of miRNA function by controlling the expression of miRNAs through a “sponging effect,” this appears to apply to only a small number of circRNAs, such as ciRS-7 acting as a miR-7 sponge (Bahn et al, 2015). It has been proposed that circRNAs may have a role in protein synthesis, with a number of circRNAs implicated in the translation of peptides, such as ZNF609 (Legnini et al, 2017). As research in this space increases, it is clear that the circRNA-miRNAmRNA network, plays an important role in both gene regulation and carcinogenesis (Su et al, 2019). CircRNAs may fulfill these roles, given their expression in PCa, in addition to studies showing circRNA such as circFOXO3 (hsa_circ_0006404) acting as an miRNA sponge in this disease (Kong et al, 2020) There is a need to identify new diagnostic and predictive biomarkers, as well as new therapeutic agents for use in the clinical setting. circRNAs may fulfill these roles, given their expression in PCa, in addition to studies showing circRNA such as circFOXO3 (hsa_circ_0006404) acting as an miRNA sponge in this disease (Kong et al, 2020)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
