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作者：SCI天天读
SCI
9 June 2023
The roles and implications of RNA m6A modification in cancer
(Nat Rev Clin OncolIF: 66.67)
Deng X, Qing Y, Horne D, Huang H, Chen J. The roles and implications of RNA m6A modification in cancer [published online ahead of print, 2023 May 23]. Nat Rev Clin Oncol. 2023;10.1038/s41571-023-00774-x. doi:10.1038/s41571-023-00774-x
N6-Methyladenosine (m6A), the most prevalent internal modification in eukaryotic mRNA, has been extensively and increasingly studied over the past decade. Dysregulation of RNA m6A modification and its associated machinery, including writers, erasers and readers, is frequently observed in various cancer types, and the dysregulation profiles might serve as diagnostic, prognostic and/or predictive biomarkers. Dysregulated m6A modifiers have been shown to function as oncoproteins or tumour suppressors with essential roles in cancer initiation, progression, metastasis, metabolism, therapy resistance and immune evasion as well as in cancer stem cell self-renewal and the tumour microenvironment, highlighting the therapeutic potential of targeting the dysregulated m6A machinery for cancer treatment. In this Review, we discuss the mechanisms by which m6A modifiers determine the fate of target RNAs and thereby influence protein expression, molecular pathways and cell phenotypes. We also describe the state-of- the-art methodologies for mapping global m6A epitranscriptomes in cancer. We further summarize discoveries regarding the dysregulation of m6A modifiers and modifications in cancer, their pathological roles, and the underlying molecular mechanisms. Finally, we discuss m6A-related prognostic and predictive molecular biomarkers in cancer as well as the development of small-molecule inhibitors targeting oncogenic m6A modifiers and their activity in preclinical models.
N6-甲基腺苷（m6A）是真核生物mRNA中最普遍的内部修饰，在过去十年中得到了广泛和日益增长的研究。在各种类型的癌症中经常观察到RNA m6A修饰及其相关机制的失调，包括写入因子、擦除因子和读取因子，而失调情况可能作为诊断、预后和/或预测的生物标志物。失调的m6A修饰物已被证明可作为癌蛋白或肿瘤抑制物，在癌症的发生、发展、转移、代谢、治疗抵抗和免疫逃避以及癌症干细胞自我更新和肿瘤微环境中发挥重要作用，突出了针对失调的m6A机制治疗癌症的潜力。在这篇综述中，我们讨论了m6A修饰剂决定目标RNA的命运，从而影响蛋白质表达、分子途径和细胞表型的机制。我们还描述了绘制癌症中全球m6A表观转录组的最新方法学。我们进一步总结了有关癌症中m6A修饰物和修饰失调的发现，它们的病理作用，以及潜在的分子机制。最后，我们讨论了癌症中与m6A相关的预后和预测分子生物标志物，以及针对致癌m6A修饰物的小分子抑制剂的开发及其在临床前模型中的活性。
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原文地址：http://mp.weixin.qq.com/s?src=11×tamp=1686378081&ver=4581&signature=DSQznJzt4rJqcQ7duyjzbuFMe5Pia4-jeBCKfxoHiB4nmqzHY09lmr7OFWo7x46qmvPMp4eW60-qKJZ2c8ezv45DcBuq*F5nzFTtplMcNFGkPdqgIIQj9UB-6n2MMcju&new=1 |
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