Greene John, Baird Anne-Marie, Brady Lauren, Lim Marvin, Gray Steven G, McDermott Raymond, Finn Stephen P
Department of Histopathology and Morbid Anatomy, School of Medicine, Trinity College DublinDublin, Ireland.
Department of Medical Oncology, Tallaght HospitalDublin, Ireland.
Front Mol Biosci. 2017 Jun 6;4:38. doi: 10.3389/fmolb.2017.00038. eCollection 2017.
Circular RNAs (circRNAs) are currently classed as non-coding RNA (ncRNA) that, unlike linear RNAs, form covalently closed continuous loops and act as gene regulators in mammals. They were originally thought to represent errors in splicing and considered to be of low abundance, however, there is now an increased appreciation of their important function in gene regulation. circRNAs are differentially generated by backsplicing of exons or from lariat introns. Unlike linear RNA, the 3' and 5' ends normally present in an RNA molecule have been joined together by covalent bonds leading to circularization. Interestingly, they have been found to be abundant, evolutionally conserved and relatively stable in the cytoplasm. These features confer numerous potential functions to circRNAs, such as acting as miRNA sponges, or binding to RNA-associated proteins to form RNA-protein complexes that regulate gene transcription. It has been proposed that circRNA regulate gene expression at the transcriptional or post-transcriptional level by interacting with miRNAs and that circRNAs may have a role in regulating miRNA function in cancer initiation and progression. circRNAs appear to be more often downregulated in tumor tissue compared to normal tissue and this may be due to (i) errors in the back-splice machinery in malignant tissues, (ii) degradation of circRNAs by deregulated miRNAs in tumor tissue, or (iii) increasing cell proliferation leading to a reduction of circRNAs. circRNAs have been identified in exosomes and more recently, chromosomal translocations in cancer have been shown to generate aberrant fusion-circRNAs associated with resistance to drug treatments. In addition, though originally thought to be non-coding, there is now increasing evidence to suggest that select circRNAs can be translated into functional proteins. Although much remains to be elucidated about circRNA biology and mechanisms of gene regulation, these ncRNAs are quickly emerging as potential disease biomarkers and therapeutic targets in cancer.
环状RNA（circRNAs）目前被归类为非编码RNA（ncRNA），与线性RNA不同，它们形成共价闭合的连续环，并在哺乳动物中充当基因调节因子。它们最初被认为是剪接错误的产物，丰度较低，然而，现在人们越来越认识到它们在基因调控中的重要功能。circRNAs通过外显子的反向剪接或套索状内含子差异生成。与线性RNA不同，RNA分子中通常存在的3'和5'末端通过共价键连接在一起，导致环化。有趣的是，它们在细胞质中含量丰富、进化保守且相对稳定。这些特性赋予circRNAs许多潜在功能，例如充当miRNA海绵，或与RNA相关蛋白结合形成调节基因转录的RNA-蛋白质复合物。有人提出，circRNA通过与miRNA相互作用在转录或转录后水平调节基因表达，并且circRNAs可能在癌症发生和发展中调节miRNA功能方面发挥作用。与正常组织相比，circRNAs在肿瘤组织中似乎更常被下调，这可能是由于：（i）恶性组织中反向剪接机制的错误；（ii）肿瘤组织中失调的miRNA对circRNAs的降解；或（iii）细胞增殖增加导致circRNAs减少。circRNAs已在外泌体中被鉴定出来，最近，癌症中的染色体易位已被证明会产生与药物治疗耐药性相关的异常融合circRNAs。此外，尽管最初认为circRNAs是非编码的，但现在越来越多的证据表明，某些circRNAs可以翻译成功能性蛋白质。尽管关于circRNA生物学和基因调控机制仍有许多有待阐明的地方，但这些ncRNAs正迅速成为癌症中潜在的疾病生物标志物和治疗靶点。
