N-Acetyltransferase 10 Promotes Gastric Cancer Progression by Mediating the N4-Acetylcytidine Modification of Lactate Dehydrogenase A

The N4-acetylcytidine (ac4C) modification, which is catalyzed by NAT10, represents a significant posttranscriptional modification of mRNA in multiple cancers. However, the significance of this modification in gastric cancer (GC) progression remains unclear. To evaluate the potential of differential NAT10 expression in GC, RT-qPCR and western blot were employed. Dot blot and acRIP were utilized for total ac4C and LDHA mRNA ac4C detection. Subsequently, the effects of NAT10 on GC cell viability and glycolysis were assessed by Cell Counting Kit-8 and glycolysis-related indicator detection Kits. Furthermore, rescue experiments and mice xenograft experiments were conducted to investigate the mechanism underlying the NAT10/LDHA signaling axis in GC. This study identified upregulated NAT10 and ac4C levels in GC. Knockdown of NAT10 led to inhibited cell viability and glycolysis. Additionally, NAT10 directly bound to LDHA mRNA. NAT10 silencing decreased the expression and stability of LDHA mRNA, as well as its ac4C modification level. Interestingly, LDHA overexpression partially reversed the effects of NAT10 knockdown on cell viability and glycolysis. Eventually, the oncogenic effect of NAT10/ac4C/LDHA axis was confirmed in xenograft experiments. NAT10 promoted the GC progression by mediating the ac4C modification of LDHA mRNA, which could serve as a potential therapeutic target for GC.