RNA editing-dependent epitranscriptome diversity in cancer stem cells.

RNA editing-dependent epitranscriptome diversity in cancer stem cells.
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DOI:
10.1038/nrc.2017.23
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发表时间:
2017-06
期刊:
Nature reviews. Cancer
影响因子:
--
通讯作者:
Jamieson CHM
Jamieson CHM
中科院分区:
其他
文献类型:
--
作者:
Jiang Q;Crews LA;Holm F;Jamieson CHM

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癌症干细胞(CSC)可以再生肿瘤的所有方面,这是由于它们具有干细胞样的自我更新,存活和在保护性微环境中休眠的能力。CSC在肿瘤进展期间以符合查尔斯达尔文的自然选择原理的方式进化。虽然体细胞DNA突变和表观遗传改变促进进化,转录后的RNA修饰与RNA结合蛋白的活性(“表转录组”)也可能有助于克隆进化,通过动态确定RNA功能和基因表达多样性,以响应环境刺激。这些表转录组事件的失调有助于CSC的产生和维持,这控制了癌症的进展和耐药性。在这篇综述中,我们讨论了恶性RNA加工在CSC生成和维持中的作用,包括RNA甲基化、RNA编辑和RNA剪接的机制,以及它们在人类恶性肿瘤中异常调节的功能后果。最后,我们强调了这些事件作为新型CSC生物标志物和治疗靶点的潜力。
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.
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