A-to-I RNA editing is an important post-transcriptional modification, known to be altered in tumors. It targets dozens of sites within miRNAs, some of which impact miRNA biogenesis and function, as well as many miRNA recognition sites. However, the full extent of the effect of editing on regulation by miRNAs and its behavior in human cancers is still unknown. Here we systematically characterized miRNA editing in 10 593 human samples across 32 cancer types and normal controls. We find that the majority of previously reported sites show little to no evidence for editing in this dataset, compile a list of 58 reliable miRNA editing sites, and study them across normal and cancer samples. Edited miRNA versions tend to suppress expression of known oncogenes, and, consistently, we observe a clear global tendency for hypo-editing in tumors, in strike contrast to the behavior for mRNA editing, allowing an accurate classification of normal/tumor samples based on their miRNA editing profile. In many cancers this profile correlates with patients' survival. Finally, thousands of miRNA binding sites are differentially edited in cancer. Our study thus establishes the important effect of RNA editing on miRNA-regulation in the tumor cell, with prospects for diagnostic and prognostic applications.

中文翻译：

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人类癌症组织表现出 miRNA 的 A-to-I 编辑减少，同时其靶标的编辑增加

A-to-I RNA 编辑是一种重要的转录后修饰，已知在肿瘤中会发生改变。它针对 miRNA 中的数十个位点，其中一些会影响 miRNA 的生物发生和功能，以及许多 miRNA 识别位点。然而，编辑对 miRNA 调控的影响及其在人类癌症中的行为的全部程度仍然未知。在这里，我们在 32 种癌症类型和正常对照的 10 593 个人类样本中系统地描述了 miRNA 编辑。我们发现大多数先前报道的位点在该数据集中几乎没有显示编辑的证据，编制了 58 个可靠 miRNA 编辑位点的列表，并在正常和癌症样本中研究它们。编辑后的 ​​miRNA 版本往往会抑制已知癌基因的表达，并且，我们始终如一地观察到肿瘤中低编辑的明显全球趋势，与 mRNA 编辑的行为形成鲜明对比，允许根据其 miRNA 编辑概况对正常/肿瘤样本进行准确分类。在许多癌症中，这种情况与患者的存活率相关。最后，数千个 miRNA 结合位点在癌症中进行了差异编辑。因此，我们的研究确定了 RNA 编辑对肿瘤细胞中 miRNA 调节的重要影响，具有诊断和预后应用的前景。