In contrast to the well-established genomic 5-methylcytosine (5mC), the existence of N⁶-methyladenine (6 mA) in eukaryotic genomes was discovered only recently. Initial studies found that it was actively regulated in cancer cells, suggesting its involvement in the process of carcinogenesis. However, the contribution of 6 mA in tongue squamous cell carcinoma (TSCC) still remains uncharacterized. In this study, a pan-cancer type analysis was first performed, which revealed enhanced 6 mA metabolism in diverse cancer types. The study was then focused on the regulation of 6 mA metabolism, as well as its effects on TSCC cells. To these aspects, genome 6 mA level was found greatly increased in TSCC tissues and cultured cells. By knocking down 6 mA methylases N6AMT1 and METTL4, the level of genomic 6 mA was decreased in TSCC cells. This led to suppressed colony formation and cell migration. By contrast, knockdown of 6 mA demethylase ALKBH1 resulted in an increased 6 mA level, enhanced colony formation, and cell migration. Further study suggested that regulation of the NF-κB pathway might contribute to the enhanced migration of TSCC cells. Therefore, in the case of TSCC, we have shown that genomic 6 mA modification is involved in the proliferation and migration of cancer cells.

与公认的基因组 5-甲基胞嘧啶 (5mC) 相比，真核基因组中 N ⁶ -甲基腺嘌呤(6 mA) 的存在直到最近才被发现。初步研究发现它在癌细胞中受到积极调节，表明它参与了癌变过程。然而，6 mA 在舌鳞状细胞癌 (TSCC) 中的作用仍未确定。在这项研究中，首先进行了泛癌类型分析，结果显示不同癌症类型中 6 mA 代谢增强。该研究随后集中在 6 mA 代谢的调节及其对 TSCC 细胞的影响。在这些方面，发现在 TSCC 组织和培养细胞中基因组 6 mA 水平大大增加。通过敲除 6 mA 甲基化酶N6AMT1和METTL4，TSCC细胞中基因组6 mA的水平降低。这导致抑制的集落形成和细胞迁移。相比之下，6 mA 去甲基化酶 ALKBH1的敲低导致 6 mA 水平增加、集落形成和细胞迁移增强。进一步的研究表明，NF-κB 通路的调节可能有助于增强 TSCC 细胞的迁移。因此，在 TSCC 的情况下，我们已经证明基因组 6 mA 修饰与癌细胞的增殖和迁移有关。