The enhanced genomic 6mA metabolism contributes to the proliferation and migration of TSCC cells

摘要

In contrast to the well-established genomic 5-methylcytosine(5mC),the existence of N^(6)-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 6mA 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 6mA level was found greatly increased in TSCC tissues and cultured cells.By knocking down 6mA methylases N6AMT1 and METTL4,the level of genomic 6mA was decreased in TSCC cells.This led to suppressed colony formation and cell migration.By contrast,knockdown of 6mA 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 6mA modification is involved in the proliferation and migration of cancer cells.