Targeting NAT10 Inhibits Hepatocarcinogenesis via ac4C-Mediated SMAD3 mRNA Stability.

ABSTRACT: Hepatocellular carcinoma (HCC) is characterized by high morbidity and mortality, with limited effective treatment options. N-acetyltransferase 10 (NAT10) is the only known acetyltransferase for mRNA ac4C modification and is recognized as a biomarker for HCC, promoting its progression. However, the critical role of NAT10 in hepatocarcinogenesis remains to be fully elucidated, and the identification of suitable small-molecule inhibitors targeting NAT10 is of great interest. Here, we report that NAT10 promotes HCC progression by stabilizing SMAD family member 3 (SMAD3) mRNA through ac4C modification. Clinically, NAT10 is highly expressed in HCC tissues and is significantly associated with poor prognosis. Functionally, NAT10 downregulation inhibits HCC cell proliferation, invasion, and

SUBMITTER: Zhang Y 

PROVIDER: S-EPMC12752639 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature