Five Circular RNAs in Metabolism Pathways Related to Prostate Cancer.

Five Circular RNAs in Metabolism Pathways Related to Prostate Cancer.
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与前列腺癌相关的代谢途径中的五种环状RNA

DOI:
10.3389/fgene.2021.636419
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发表时间:
2021
影响因子:
3.7
通讯作者:
Zhang Y
Zhang Y
中科院分区:
生物学3区
文献类型:
--
作者:
Zhang L;Zhang W;Li H;Tang X;Xu S;Wu M;Wan L;Su F;Zhang Y

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前列腺癌(PCa)是男性最常见的恶性肿瘤,其发病率随年龄增长而增加。血清前列腺特异性抗原和组织活检仍然是诊断可疑PCa的标准。然而,这些临床指标可能会导致积极监测已得到充分治疗的患者过度治疗。环状RNA(CircRNA)是近年来发现的一种新型的调控RNA,由于其共价闭合的环状结构,不易被RNA酶和其他核酸外切酶降解。因此,我们利用高通量测序数据和生物信息学分析来鉴定PCa中特异性表达的circRNA,并筛选出五种特异性circRNA用于进一步分析-hsa_circ_0006410、hsa_circ_0003970、hsa_circ_0006754、hsa_circ_0005848和一种新型circRNA hsa_circ_AKAP7。我们构建了一个circRNA-miRNA调控网络,并使用miRNA和差异表达的mRNA相互作用来预测所选circRNA的功能。此外,同源基因的存活分析和PCR验证表明,这五个circRNA与众所周知的PCa通路如MAPK信号通路、P53通路、雄激素受体信号通路、细胞周期、细胞色素介导的信号通路和细胞脂质代谢过程密切相关。通过了解circRNA的相关代谢,这些circRNA可以作为代谢生物标志物,监测它们的水平可以帮助诊断PCa。同时,在PCa中AR相关调节的确切调节机制仍不清楚。我们发现的circRNA可以为该领域的研究提供新的解决方案。
Prostate cancer (PCa) is the most common malignant tumor in men, and its incidence increases with age. Serum prostate-specific antigen and tissue biopsy remain the standard for diagnosis of suspected PCa. However, these clinical indicators may lead to aggressive overtreatment in patients who have been treated sufficiently with active surveillance. Circular RNAs (circRNAs) have been recently recognized as a new type of regulatory RNA that is not easily degraded by RNases and other exonucleases because of their covalent closed cyclic structure. Thus, we utilized high-throughput sequencing data and bioinformatics analysis to identify specifically expressed circRNAs in PCa and filtered out five specific circRNAs for further analysis—hsa_circ_0006410, hsa_circ_0003970, hsa_circ_0006754, hsa_circ_0005848, and a novel circRNA, hsa_circ_AKAP7. We constructed a circRNA-miRNA regulatory network and used miRNA and differentially expressed mRNA interactions to predict the function of the selected circRNAs. Furthermore, survival analysis of their cognate genes and PCR verification of these five circRNAs revealed that they are closely related to well-known PCa pathways such as the MAPK signaling pathway, P53 pathway, androgen receptor signaling pathway, cell cycle, hormone-mediated signaling pathway, and cellular lipid metabolic process. By understanding the related metabolism of circRNAs, these circRNAs could act as metabolic biomarkers, and monitoring their levels could help diagnose PCa. Meanwhile, the exact regulatory mechanism for AR-related regulation in PCa is still unclear. The circRNAs we found can provide new solutions for research in this field.
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