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细化 N6-甲基腺苷在癌症中的作用。

Refining the role of N-methyladenosine in cancer.

机构信息

Division of Epigenetics, DKFZ-ZMBH Alliance, German Cancer Research Center, 69120 Heidelberg, Germany.

Division of Epigenetics, DKFZ-ZMBH Alliance, German Cancer Research Center, 69120 Heidelberg, Germany.

出版信息

Curr Opin Genet Dev. 2024 Oct;88:102242. doi: 10.1016/j.gde.2024.102242. Epub 2024 Aug 6.

Abstract

N-methyladenosine (mA) is the most abundant internal modification of eukaryotic mRNAs. mA affects the fate of its targets in all aspects of the mRNA life cycle and has important roles in various physiological and pathophysiological processes. Aberrant mA patterns have been observed in numerous cancers and appear closely linked to oncogenic phenotypes. However, most studies relied on antibody-dependent modification detection, which is known to suffer from important limitations. Novel, antibody-independent, quantitative approaches will be critical to investigate changes in the mA landscape of cancers. Furthermore, pharmaceutical targeting of the mA writer Methyltransferase-like 3 (METTL3) has demonstrated the potential to modulate cancer cell phenotypes. However, the enzyme also appears to be essential for the viability of healthy cells. Further refinement of therapeutic strategies is therefore needed to fully realize the potential of mA-related cancer therapies.

摘要

N6-甲基腺苷(m6A)是真核 mRNA 中最丰富的内部修饰。m6A 影响其靶标在 mRNA 生命周期的各个方面的命运,并且在各种生理和病理生理过程中具有重要作用。在许多癌症中都观察到异常的 m6A 模式,并且似乎与致癌表型密切相关。然而,大多数研究依赖于抗体依赖性修饰检测,众所周知,这种方法存在重要的局限性。新型、抗体非依赖性、定量方法对于研究癌症中 m6A 图谱的变化至关重要。此外,靶向甲基转移酶样 3(METTL3)的药物治疗已证明有潜力调节癌细胞表型。然而,该酶似乎对健康细胞的活力也是必需的。因此,需要进一步完善治疗策略,以充分实现 m6A 相关癌症治疗的潜力。

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