Greene John, Baird Anne-Marie, Lim Marvin, Flynn Joshua, McNevin Ciara, Brady Lauren, Sheils Orla, Gray Steven G, McDermott Raymond, Finn Stephen P
Department of Histopathology and Morbid Anatomy, School of Medicine, Trinity College, Dublin, Ireland.
Department of Medical Oncology, Tallaght University Hospital, Dublin, Ireland.
Front Cell Dev Biol. 2021 Feb 25;9:605686. doi: 10.3389/fcell.2021.605686. eCollection 2021.
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 ( = 9). circRNAs were more commonly significantly up-regulated ( < 0.05) than downregulated in malignant cell lines ( = 3,409) vs. benign cell lines ( = 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 , and hsa_circ_0060539, whose predicted gene target is . Furthermore, we identified three circRNAs associated with the parental gene (hsa_circ_0021652, hsa_circ_0000288, and hsa_circ_0021647). Other studies have shown the importance of 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.
环状RNA(circRNAs)是最近发现的一种非编码RNA,具有多种功能,包括调节miRNA表达。它们已在包括前列腺癌(PCa)在内的多种恶性肿瘤中被检测到。本研究调查了与PCa和雄激素受体(AR)状态相关的circRNAs的差异表达模式。使用高通量微阵列分析对一组前列腺细胞系进行circRNA谱分析,该细胞系由正常、良性和恶性细胞组成(n = 9)。与良性细胞系(n = 2,949)相比,恶性细胞系(n = 3,409)中circRNAs更常显著上调(P < 0.05)而非下调。在基于AR状态的分组分析中,雄激素非依赖性细胞系中有2,127个下调的circRNAs,而雄激素依赖性细胞系中有2,236个,从而确定了一个反映雄激素依赖性的潜在circRNA特征。通过生物信息学方法,鉴定了与前10个差异表达的circRNAs相关的亲本基因,如hsa_circ_0064644,其预测的亲本基因靶点是[具体基因名称未给出],以及hsa_circ_0060539,其预测的基因靶点是[具体基因名称未给出]。此外,我们鉴定了与亲本基因[具体基因名称未给出]相关的三个circRNAs(hsa_circ_0021652、hsa_circ_0000288和hsa_circ_0021647)。其他研究表明[具体基因名称未给出]在PCa细胞存活和耐药性中的重要性。鉴于此处鉴定出的circRNA表达特征的改变,这些产生假设的结果表明circRNAs可能作为PCa中潜在的诊断和预测标志物。然而,需要进一步的验证研究来评估这些标志物在临床环境中的真正潜力。