Circular RNA (circRNA) is a group of RNA families generated by RNA circularization, which was discovered ubiquitously across different cancers. However, the internal structure of circRNA is difficult to determine due to alternative splicing that occurs in its exons and introns. Furthermore, cancer-specific alternative splicing of circRNA is less likely to be identified. Here, we proposed a de novo algorithm, CircSplice, that could identify internal alternative splicing in circRNA and compare differential circRNA splicing events between different conditions ( http://gb.whu.edu.cn/CircSplice or https://github.com/GeneFeng/CircSplice ). By applying CircSplice in clear cell renal cell carcinoma and bladder cancer, we detected 4498 and 2977 circRNA alternative splicing (circ-AS) events in the two datasets respectively and confirmed the expression of circ-AS events by RT-PCR. We further inspected the distributions and patterns of circ-AS in cancer and adjacent normal tissues. To further understand the potential functions of cancer-specific circ-AS, we classified those events into tumor suppressors and oncogenes and performed pathway enrichment analysis. This study is the first comprehensive view of cancer-specific circRNA alternative splicing, which could contribute significantly to regulation and functional research of circRNAs in cancers.

中文翻译：

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circRNA中癌症特异性替代剪接的全基因组鉴定。

环状RNA（circRNA）是由RNA环化产生的一组RNA家族，广泛发现于不同的癌症中。然而，由于在其外显子和内含子中出现的可变剪接，很难确定circRNA的内部结构。此外，不太可能发现circRNA的癌症特异性替代剪接。在这里，我们提出了一个从头算法CircSplice，该算法可以识别circRNA中的内部替代剪接并比较不同条件之间的差异性circRNA剪接事件（http://gb.whu.edu.cn/CircSplice或https://github.com / GeneFeng / CircSplice）。通过将CircSplice用于透明细胞肾细胞癌和膀胱癌，我们在两个数据集中分别检测到4498和2977个circRNA选择性剪接（circ-AS）事件，并通过RT-PCR确认了circ-AS事件的表达。我们进一步检查了circ-AS在癌症和邻近正常组织中的分布和模式。为了进一步了解特定于癌症的circ-AS的潜在功能，我们将这些事件分类为肿瘤抑制因子和致癌基因，并进行了途径富集分析。这项研究是癌症特异性circRNA选择性剪接的第一个综合观点，可为癌症中circRNA的调控和功能研究做出重要贡献。我们将这些事件分为肿瘤抑制因子和致癌基因，并进行了途径富集分析。这项研究是癌症特异性circRNA选择性剪接的第一个综合观点，可为癌症中circRNA的调控和功能研究做出重要贡献。我们将这些事件分为肿瘤抑制因子和致癌基因，并进行了途径富集分析。这项研究是癌症特异性circRNA选择性剪接的第一个综合观点，可为癌症中circRNA的调控和功能研究做出重要贡献。