NAT10 Promotes Prostate Cancer Growth and Metastasis by Acetylating mRNAs of HMGA1 and KRT8

N4‐acetylcytidine (ac4C) is essential for the development and migration of tumor cells. According to earlier research, N‐acetyltransferase 10 (NAT10) can increase messenger RNAs (mRNAs) stability by catalyzing the synthesis of ac4C. However, little is known about NAT10 expression and its role in the acetylation modifications in prostate cancer (PCa). Thus, the biological function of NAT10 in PCa is investigated in this study. Compared to paraneoplastic tissues, the expression of NAT10 is significantly higher in PCa. The NAT10 expression is strongly correlated with the pathological grade, clinical stage, Gleason score, T‐stage, and N‐stage of PCa. NAT10 has the ability to advance the cell cycle and the epithelial‐mesenchymal transition (EMT), both of which raise the malignancy of tumor cells. Mechanistically, NAT10 enhance the stability of high mobility group AT‐hook 1 (HMGA1) by acetylating its mRNA, thereby promoting cell cycle progression to improve cell proliferation. In addition, NAT10 improve the stability of Keratin 8 (KRT8) by acetylating its mRNA, which promotes the progression of EMT to improve cell migration. This findings provide a potential prognostic or therapeutic target for PCa. Increased NAT10 expression accounted for inferior clinicopathological characteristics in patients with PCa. NAT10 can promote prostate cancer growth and metastasis by catalyzing the formation of ac4C. Mechanistically, NAT10 enhance the stability of HMGA1 by acetylating its mRNA, thereby promoting cell cycle progression to improve cell proliferation. In addition, NAT10 improve the stability of KRT8 by acetylating its mRNA, which promotes the progression of epithelial‐mesenchymal transition to improve cell migration.