Abstract

Background N-acetyltransferase 10 (NAT10) mediated N 4 -acetylcytidine (ac 4 C) modification is a significant RNA modification in various tumors. This study aimed to investigate the underlying mechanism of NAT10 modulating the progression of colorectal cancer via mRNA ac 4 C modification. Methods Aberrant expressed NAT10 in colorectal cancer was identified from GSE37182 dataset. The ac 4 C modification levels in colorectal cancer cells were accessed by dot blotting assay, and the NAT10 levels were accessed by RT-qPCR. Cell viability, proliferation, invasion, and migration of colorectal cancer cells were evaluated to determine the regulatory role of NAT10 on cell aggressiveness. The interaction between NAT10 and Serine protease inhibitor A1 (SERPINA1) was verified using RNA immunoprecipitation (RIP) and ac 4 C RNA immunoprecipitation (ac 4 C RIP), and Luciferase reporter assay. Moreover, the regulatory role of NAT10 on tumorigenesis of colorectal cancer cells in vivo was investiaged in xenograft tumor model. Results Global ac 4 C modification and NAT10 expression were significantly elevated in colorectal cancer cells.. Down-regulation of NAT10 inhibited cell proliferation, invasion, and migration of colorectal cancer cells. Mechanistically, NAT10 bound directly to SERPINA1 mRNA and enhanced its ac 4 C modification, thereby increasing its stability. This regulation was proven to be ac 4 C-dependent. Over-expression of SERPINA1 partially weakened the suppression effects of NAT10 knockdown on aggressiveness of colorectal cancer cells. Furthermore, pharmacological inhibition of NAT10 significantly suppressed tumor growth in vivo. Conclusion Our findings demonstrate that NAT10 promotes the aggressiveness of colorectal cancer cells by regulating the ac 4 C modification of SERPINA1 mRNA, highlighting this axis as a potential therapeutic target.