biostudies-literatureUnknown9(1)Pan ZEmerging evidence showed that epigenetic regulation plays important role in the pathogenesis of HCC. N4-acetocytidine (ac4C) was an acetylation chemical modification of mRNA, and NAT10 is reported to regulate ac4C modification and enhance endoplasmic reticulum stress (ERS) in tumor metastasis. Here, we report a novel mechanism by which NAT10-mediated mRNA ac4C-modified HSP90AA1 regulates metastasis and tumor resistance in ERS of HCC. Immunohistochemical, bioinformatics analyses, and in vitro and in vivo experiments, e.g., acRIP-Seq, RNA-Seq, and double luciferase reporter experiment, were employed to investigate the effect of NAT10 on metastasis and drug resistance in HCC. The increased expression of NAT10 was associated with HCC risk and poor prognosis. Cell and animal experiments showed Cell death discoveryhttps://www.ebi.ac.uk/biostudies/studies/S-EPMC9918514biostudies-literatureRole of NAT10-mediated ac4C-modified HSP90AA1 RNA acetylation in ER stress-mediated metastasis and lenvatinib resistance in hepatocellular carcinomaPMC9918514Pan ZWang AZhu YBao YFan LCui JHu MTan CSun GYu HfalseRole of NAT10-mediated ac4C-modified HSP90AA1 RNA acetylation in ER stress-mediated metastasis and lenvatinib resistance in hepatocellular carcinomaEmerging evidence showed that epigenetic regulation plays important role in the pathogenesis of HCC. N4-acetocytidine (ac4C) was an acetylation chemical modification of mRNA, and NAT10 is reported to regulate ac4C modification and enhance endoplasmic reticulum stress (ERS) in tumor metastasis. Here, we report a novel mechanism by which NAT10-mediated mRNA ac4C-modified HSP90AA1 regulates metastasis and tumor resistance in ERS of HCC. Immunohistochemical, bioinformatics analyses, and in vitro and in vivo experiments, e.g., acRIP-Seq, RNA-Seq, and double luciferase reporter experiment, were employed to investigate the effect of NAT10 on metastasis and drug resistance in HCC. The increased expression of NAT10 was associated with HCC risk and poor prognosis. Cell and animal experiments showed 2023-01-01T00:00:00Z2023 Jan2025-04-18T15:52:07.468Z2025-02-19T02:56:44.042ZS-EPMC9918514