NAT10通过调节ac4C-DDIAS-PI3K-Akt轴促进肝细胞癌进展。

NAT10 promotes hepatocellular carcinoma progression by modulating the ac4C-DDIAS-PI3K-Akt axis.

作者信息

Tao Yue, Wang Leisheng, Chen Enhong, Zhang Shuo, Yang Dongjie, Chen Wuqiang, He Youzhao, Gu Yuanlong, Mao Yong, Hu Hao

机构信息

Wuxi Medical College, Jiangnan University, Wuxi, 214122, Jiangsu Province, China.

Wuxi Ninth People's Hospital Affiliated to Soochow University, No.999 Liangxi Road, Binhu District, Wuxi, China.

出版信息

Sci Rep. 2025 May 19;15(1):17286. doi: 10.1038/s41598-025-00707-x.

DOI:10.1038/s41598-025-00707-x

PMID:40389420

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12089488/

Abstract

Primary liver cancer (PLC) is a prevalent tumor globally, ranking third in cancer-related mortality. The role of N4-acetylcysteine (ac4C) and N-acetyltransferase 10 (NAT10) in hepatocellular carcinoma (HCC) progression, migration, and invasion requires further elucidation. High NAT10 expression correlated with poor prognosis in HCC patients. Knockdown of NAT10 hindered HCC cell proliferation. AcRIP-seq screening revealed DDIAS as a significant downstream target of NAT10. Decreased NAT10 levels reduced DDIAS mRNA stability, leading to decreased proliferation, migration, and invasion of HCC cells upon DDIAS knockdown. Ectopic expression of DDIAS counteracted the effects of NAT10 knockdown by modulating the PI3K/AKT pathway. NAT10 was found to be elevated in HCC tissues compared to normal tissues, promoting HCC progression and correlating with shorter overall survival in patients. Mechanistically, NAT10 regulated HCC progression through the ac4C-DDIAS-PI3K-AKT axis.

摘要

原发性肝癌（PLC）是全球范围内一种常见的肿瘤，在癌症相关死亡率中排名第三。N4-乙酰半胱氨酸（ac4C）和N-乙酰转移酶10（NAT10）在肝细胞癌（HCC）进展、迁移和侵袭中的作用需要进一步阐明。NAT10高表达与HCC患者的不良预后相关。敲低NAT10会阻碍HCC细胞增殖。AcRIP-seq筛选显示DDIAS是NAT10的一个重要下游靶点。NAT10水平降低会降低DDIAS mRNA稳定性，导致敲低DDIAS后HCC细胞的增殖、迁移和侵袭减少。DDIAS的异位表达通过调节PI3K/AKT途径抵消了NAT10敲低的影响。与正常组织相比，HCC组织中NAT10升高，促进HCC进展，并与患者较短的总生存期相关。从机制上讲，NAT10通过ac4C-DDIAS-PI3K-AKT轴调节HCC进展。