Hypoxia is associated with several diseases, including cancer. Cells that are deprived of adequate oxygen supply trigger transcriptional and post-transcriptional responses, which control cellular pathways such as angiogenesis, proliferation, and metabolic adaptation. Circular RNAs (circRNAs) are a novel class of mainly non-coding RNAs, which have been implicated in multiple cancers and attract increasing attention as potential biomarkers. Here, we characterize the circRNA signatures of three different cancer cell lines from cervical (HeLa), breast (MCF-7), and lung (A549) cancer under hypoxia. In order to reliably detect circRNAs, we integrate available tools with custom approaches for quantification and statistical analysis. Using this consolidated computational pipeline, we identify ~12000 circRNAs in the three cancer cell lines. Their molecular characteristics point to an involvement of complementary RNA sequences as well as trans-acting factors in circRNA biogenesis, such as the RNA-binding protein HNRNPC. Notably, we detect a number of circRNAs that are more abundant than their linear counterparts. In addition, 64 circRNAs significantly change in abundance upon hypoxia, in most cases in a cell type-specific manner. In summary, we present a comparative circRNA profiling in human cancer cell lines, which promises novel insights into the biogenesis and function of circRNAs under hypoxic stress.

中文翻译：

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一种组合的计算管道，可在缺氧胁迫下检测人类癌细胞中的环状RNA。

缺氧与多种疾病有关，包括癌症。被剥夺足够氧气供应的细胞会触发转录和转录后反应，从而控制诸如血管生成，增殖和代谢适应等细胞途径。环状RNA（circRNA）是一类主要是非编码RNA的新型类别，已与多种癌症有关，并作为潜在的生物标记物引起了越来越多的关注。在这里，我们表征了缺氧条件下宫颈癌（HeLa），乳腺癌（MCF-7）和肺癌（A549）三种不同癌细胞系的circRNA特征。为了可靠地检测circRNA，我们将可用工具与自定义方法集成在一起进行定量和统计分析。使用这种整合的计算流程，我们在这三种癌细胞系中鉴定了约12000个circRNA。circRNA生物发生中的反式作用因子，例如RNA结合蛋白HNRNPC。值得注意的是，我们检测到了许多circRNA，它们比其线性对应物更为丰富。另外，在大多数情况下，缺氧条件下64种circRNA的丰度会发生显着变化，大多数情况下会以细胞类型特异性的方式发生变化。总而言之，我们提出了在人类癌细胞系中进行circRNA的比较分析，这有望在缺氧胁迫下对circRNA的生物发生和功能产生新的见解。