Dragomir Mihnea, Calin George A
Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.
Research Center for Functional Genomics, Biomedicine and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
Front Oncol. 2018 May 28;8:179. doi: 10.3389/fonc.2018.00179. eCollection 2018.
Circular RNAs (circRNA) are RNA molecules built from fragments of linear pre-messenger RNAs and other linear RNA species through a process termed "back-splicing" in which the 3' and 5' ends are joined together giving rise to a covalently uninterrupted loop. circRNAs are not new members of the RNA world; they were first discovered in the early 1990s. The novelty is their abundance in the mammalian cells, as recently thousands of circRNAs were discovered and annotated. The biogenesis of circRNAs is a partially characterized process, regulated by three different mechanisms: exon skipping, intron pairing, and RNA-binding proteins. On the other hand, the function of circRNAs remains largely unknown and only a handful of singular reports describe in detail the biological roles of some circular transcripts. In a very short period of time, numerous circRNAs were associated with various cancer types and were also identified in bodily fluids with the potential of being disease-specific biomarkers. In this review, we briefly describe the biogenesis and function of circRNAs and present the circular transcripts that were more than once reported in literature to be associated with cancer. Finally, we point out some of the difficulties encountered in the study of circRNAs in cancer, as we consider that taking these into account could accelerate and improve our understanding of the biologic and translational use of circRNAs in human diseases.
环状RNA（circRNA）是由线性前体信使RNA和其他线性RNA分子片段通过一种称为“反向剪接”的过程构建而成的RNA分子，在该过程中，3'端和5'端连接在一起，形成一个共价不间断的环。circRNA并非RNA世界的新成员；它们于20世纪90年代初首次被发现。新颖之处在于它们在哺乳动物细胞中的丰度，因为最近发现并注释了数千种circRNA。circRNA的生物合成是一个部分特征化的过程，受三种不同机制调控：外显子跳跃、内含子配对和RNA结合蛋白。另一方面，circRNA的功能在很大程度上仍然未知，只有少数单独的报告详细描述了一些环状转录本的生物学作用。在很短的时间内，大量circRNA与各种癌症类型相关联，并且在体液中也被鉴定出来，具有作为疾病特异性生物标志物的潜力。在这篇综述中，我们简要描述了circRNA的生物合成和功能，并介绍了文献中不止一次报道与癌症相关的环状转录本。最后，我们指出了在癌症circRNA研究中遇到的一些困难，因为我们认为考虑这些因素可以加速并提高我们对circRNA在人类疾病中的生物学和转化应用的理解。
