文章：

癌症干细胞中RNA编辑依赖的表转录组多样性

RNA editing-dependent epitranscriptome diversity in cancer stem cells

原文发布日期：2017-04-18

DOI: 10.1038/nrc.2017.23

类型: Review Article

开放获取: 否

要点：

1. Methylation of RNA at N⁶-methyladenosine (m⁶A) has been identified in humans, viruses and mice and has been linked to several diseases.
2. m⁶A plays an important role in pluripotency and differentiation and has therefore been associated with cancer development; it can promote the translation of several oncogenes.
3. Malignant adenosine-to-inosine RNA editing controls the self-renewal of cancer stem cells (CSCs), and raises the possibility that targeting this pathway may provide a new strategy for eliminating CSCs.
4. RNA splicing disruption promotes generation of aberrant splice isoforms in pre-malignant and malignant haematopoietic disorders and is a key therapeutic vulnerability in a growing number of human malignancies.
5. Therapeutic splicing modulation has the potential to target bulk tumour cells as well as self-renewing CSCs that contribute to disease progression and relapse.

要点翻译：

1. N6-甲基腺嘌呤（m6A）RNA甲基化修饰已在人类、病毒和小鼠中被发现，并与多种疾病相关。
2. m6A在细胞多能性与分化过程中发挥重要作用，因此与癌症发展密切相关——它能促进多种癌基因的翻译表达。
3. 恶性腺苷至肌苷的RNA编辑调控着癌症干细胞（CSCs）的自我更新能力，这提示靶向该通路可能为清除CSCs提供新策略。
4. RNA剪接紊乱会促进癌前及恶性造血系统疾病中异常剪接亚型的产生，且已成为越来越多人类恶性肿瘤的关键治疗靶点。
5. 治疗性剪接调控不仅有望靶向主体肿瘤细胞，还能针对导致疾病进展与复发的自我更新型癌症干细胞。

英文摘要：

Cancer stem cells (CSCs) can regenerate all facets of a tumour as a result of their stem cell-like capacity to self-renew, survive and become dormant in protective microenvironments. CSCs evolve during tumour progression in a manner that conforms to Charles Darwin's principle of natural selection. Although somatic DNA mutations and epigenetic alterations promote evolution, post-transcriptional RNA modifications together with RNA binding protein activity (the 'epitranscriptome') might also contribute to clonal evolution through dynamic determination of RNA function and gene expression diversity in response to environmental stimuli. Deregulation of these epitranscriptomic events contributes to CSC generation and maintenance, which governs cancer progression and drug resistance. In this Review, we discuss the role of malignant RNA processing in CSC generation and maintenance, including mechanisms of RNA methylation, RNA editing and RNA splicing, and the functional consequences of their aberrant regulation in human malignancies. Finally, we highlight the potential of these events as novel CSC biomarkers as well as therapeutic targets.

摘要翻译： 

癌症干细胞（CSC）因其类干细胞的自我更新、存活以及在保护性微环境中进入休眠的能力，能够再生肿瘤的所有方面。CSC在肿瘤进展过程中遵循查尔斯·达尔文自然选择原理不断演化。尽管体细胞DNA突变和表观遗传改变促进其进化，但转录后RNA修饰及RNA结合蛋白活性（即“表观转录组”）也可能通过动态决定RNA功能和环境刺激下的基因表达多样性，促进克隆进化。这些表观转录组事件的失调促进CSC的产生与维持，从而控制癌症进展和耐药性。本综述探讨了恶性RNA加工在CSC生成与维持中的作用，包括RNA甲基化、RNA编辑和RNA剪接机制，以及其异常调控在人类恶性肿瘤中的功能后果。最后，我们强调了这些事件作为新型CSC生物标志物及治疗靶点的潜力。

原文链接：

RNA editing-dependent epitranscriptome diversity in cancer stem cells