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m6A RNA 甲基化调控致癌信号通路,驱动细胞恶性转化和癌变。

The mA RNA methylation regulates oncogenic signaling pathways driving cell malignant transformation and carcinogenesis.

机构信息

Division of Cancer Biology, Department of Medicine, MetroHealth Medical Center, Case Western Reserve University School of Medicine, Cleveland, OH, 44109, USA.

出版信息

Mol Cancer. 2021 Apr 4;20(1):61. doi: 10.1186/s12943-021-01356-0.

Abstract

The mA RNA methylation is the most prevalent internal modification in mammalian mRNAs which plays critical biological roles by regulating vital cellular processes. Dysregulations of the mA modification due to aberrant expression of its regulatory proteins are frequently observed in many pathological conditions, particularly in cancer. Normal cells undergo malignant transformation via activation or modulation of different oncogenic signaling pathways through complex mechanisms. Accumulating evidence showing regulation of oncogenic signaling pathways at the epitranscriptomic level has added an extra layer of the complexity. In particular, recent studies demonstrated that, in many types of cancers various oncogenic signaling pathways are modulated by the mA modification in the target mRNAs as well as noncoding RNA transcripts. mA modifications in these RNA molecules control their fate and metabolism by regulating their stability, translation or subcellular localizations. In this review we discussed recent exciting studies on oncogenic signaling pathways that are modulated by the mA RNA modification and/or their regulators in cancer and provided perspectives for further studies. The regulation of oncogenic signaling pathways by the mA modification and its regulators also render them as potential druggable targets for the treatment of cancer.

摘要

m6A 甲基化是哺乳动物 mRNA 中最普遍的内部修饰,通过调节重要的细胞过程发挥关键的生物学作用。由于其调节蛋白的异常表达,m6A 修饰的失调在许多病理条件下经常观察到,特别是在癌症中。正常细胞通过通过复杂的机制激活或调节不同的致癌信号通路经历恶性转化。越来越多的证据表明,在许多类型的癌症中,致癌信号通路在转录后水平受到调节,这增加了复杂性的另一层。特别是,最近的研究表明,在许多类型的癌症中,各种致癌信号通路被靶 mRNA 中的 m6A 修饰以及非编码 RNA 转录物调节。这些 RNA 分子中的 m6A 修饰通过调节它们的稳定性、翻译或亚细胞定位来控制它们的命运和代谢。在这篇综述中,我们讨论了最近关于致癌信号通路的激动人心的研究,这些通路被 m6A RNA 修饰和/或它们在癌症中的调节剂所调节,并为进一步的研究提供了观点。致癌信号通路的 m6A 修饰及其调节剂的调节也使它们成为癌症治疗的潜在可药用靶标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0b4/8019509/2ecb8a673a61/12943_2021_1356_Fig1_HTML.jpg

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