Jiang Qingfei, Crews Leslie A, Holm Frida, Jamieson Catriona H M
Division of Regenerative Medicine, Department of Medicine, Moores Cancer Center and Sanford Consortium for Regenerative Medicine, University of California, San Diego, La Jolla, California 92093, USA.
Nat Rev Cancer. 2017 Jun;17(6):381-392. doi: 10.1038/nrc.2017.23. Epub 2017 Apr 18.
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.
癌症干细胞（CSCs）由于其具有类似干细胞的自我更新、存活以及在保护性微环境中进入休眠状态的能力，能够再生肿瘤的各个方面。癌症干细胞在肿瘤进展过程中的演变方式符合查尔斯·达尔文的自然选择原则。虽然体细胞DNA突变和表观遗传改变促进了进化，但转录后RNA修饰以及RNA结合蛋白活性（“表观转录组”）也可能通过动态决定RNA功能和基因表达多样性以响应环境刺激，从而对克隆进化有所贡献。这些表观转录组事件的失调会导致癌症干细胞的产生和维持，进而控制癌症进展和耐药性。在本综述中，我们讨论了恶性RNA加工在癌症干细胞产生和维持中的作用，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控的功能后果。最后，我们强调了这些事件作为新型癌症干细胞生物标志物以及治疗靶点的潜力。
