Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA; Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Biosciences and Bioengineering, Indian Institute of Technology Dharwad, Dharwad, 580011, India.
Cell. 2019 Feb 7;176(4):869-881.e13. doi: 10.1016/j.cell.2018.12.021.
Circular RNAs (circRNAs) are an intriguing class of RNA due to their covalently closed structure, high stability, and implicated roles in gene regulation. Here, we used an exome capture RNA sequencing protocol to detect and characterize circRNAs across >2,000 cancer samples. When compared against Ribo-Zero and RNase R, capture sequencing significantly enhanced the enrichment of circRNAs and preserved accurate circular-to-linear ratios. Using capture sequencing, we built the most comprehensive catalog of circRNA species to date: MiOncoCirc, the first database to be composed primarily of circRNAs directly detected in tumor tissues. Using MiOncoCirc, we identified candidate circRNAs to serve as biomarkers for prostate cancer and were able to detect circRNAs in urine. We further detected a novel class of circular transcripts, termed read-through circRNAs, that involved exons originating from different genes. MiOncoCirc will serve as a valuable resource for the development of circRNAs as diagnostic or therapeutic targets across cancer types.
环状 RNA（circRNAs）是一类具有吸引力的 RNA，因为它们具有共价闭合的结构、高度稳定性，并在基因调控中发挥作用。在这里，我们使用外显子捕获 RNA 测序方案在 >2000 个癌症样本中检测和表征 circRNAs。与 Ribo-Zero 和 RNase R 相比，捕获测序显著提高了 circRNAs 的富集度，并保持了准确的环状到线性比值。使用捕获测序，我们构建了迄今为止最全面的 circRNA 物种目录：MiOncoCirc，这是第一个主要由肿瘤组织中直接检测到的 circRNAs 组成的数据库。使用 MiOncoCirc，我们确定了候选 circRNAs 作为前列腺癌的生物标志物，并能够在尿液中检测到 circRNAs。我们进一步检测到一类新的环状转录本，称为读通 circRNAs，它们涉及来自不同基因的外显子。MiOncoCirc 将成为开发跨癌症类型的诊断或治疗靶点的 circRNAs 的有价值的资源。
