NAT10 promotes proliferation, invasion, and epithelial-mesenchymal transition in hepatocellular carcinoma through α-tubulin acetylation.

Hepatocellular carcinoma (HCC) remains a global health challenge due to its high metastatic potential and poor prognosis. This study investigated the role and underlying molecular mechanisms of N-acetyltransferase 10 (NAT10)-mediated α-tubulin acetylation in HCC progression. Using Huh-7 and SNU-449 cell lines, we established stable knockdown and overexpression models to systematically evaluate both gain- and loss-of-function effects. Functional assays revealed that NAT10 suppression significantly decreased α-tubulin acetylation, thereby inhibiting cell proliferation, invasion, and migration. Conversely, NAT10 overexpression promoted these oncogenic traits. In vivo validation confirmed NAT10 accelerates tumor growth and lung metastasis. Treatment with the NAT10 inhibitor Remodelin partially reversed the phenotypic effects of NAT10 overexpression and restored epithelial - mesenchymal transition (EMT) marker expression. In conclusion, our results demonstrate that NAT10 drives HCC progression by regulating the α-tubulin acetylation axis, highlighting its potential as a promising therapeutic target for combating HCC metastasis.