Despite their small numbers, cancer stem cells play a central role in driving cancer cell growth, chemotherapeutic resistance, and distal metastasis. Previous studies mainly focused on how DNA or histone modification determines cell fate in cancer. However, it is still largely unknown how RNA modifications orchestrate cancer cell fate decisions. More than 170 distinct RNA modifications have been identified in the RNA world, while only a few RNA base modifications have been found in mRNA. Growing evidence indicates that three mRNA modifications, inosine, 5-methylcytosine, and N6-methyladenosine, are essential for the regulation of spatiotemporal gene expression during cancer stem cell fate transition. Furthermore, transcriptome-wide mapping has found that the aberrant deposition of mRNA modification, which can disrupt the gene regulatory network and lead to uncontrollable cancer cell growth, is widespread across different cancers. In this review, we try to summarize the recent advances of these three mRNA modifications in maintaining the stemness of cancer stem cells and discuss the underlying molecular mechanisms, which will shed light on the development of novel therapeutic approaches for eradicating cancer stem cells.

中文翻译：

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mRNA修饰可协调癌症干细胞的命运决定。

尽管数量少，但是癌症干细胞在驱动癌细胞生长，化疗耐药性和远端转移中起着核心作用。先前的研究主要集中于DNA或组蛋白修饰如何决定癌症中的细胞命运。然而，在很大程度上，RNA修饰如何协调癌细胞的命运决定仍是未知数。在RNA世界中已鉴定出170多种不同的RNA修饰，而在mRNA中仅发现了少数RNA碱基修饰。越来越多的证据表明，肌苷，5-甲基胞嘧啶和N6-甲基腺苷这三种mRNA修饰对于癌症干细胞命运转变过程中时空基因表达的调节至关重要。此外，整个转录组定位已发现mRNA修饰的异常沉积，它可以破坏基因调控网络并导致不可控制的癌细胞生长，在不同的癌症中广泛存在。在这篇综述中，我们试图总结这三种mRNA修饰在维持癌症干细胞干性方面的最新进展，并讨论其潜在的分子机制，这将为消灭癌症干细胞的新型治疗方法的发展提供启示。