Fig. 7: Targeting METTL3 O-GlcNAcylation suppresses its oncogenic role in HCC.

A Schematic representations of the CPPtat-M1, CPPtat-M2, and CPPtat-M2 mut peptides. Differential residues are highlighted in red. B, C Huh-7 cells were treated with CPPtat, CPPtat-M1, CPPtat-M2, or CPPtat-M2 mut (10 µM) for 24 h, followed by an sWGA pull-down assay to asses METTL3 O-GlcNAcylation. CPPtat-, CPPtat-M2-, CPPtat-M2 mut-treated cells were subjected to CCK-8 (D), colony formation (E), Transwell (F, scale bar: 100 μm), and wound-healing (G, scale bar: 200 μm) assays. Representative images from three independent experiments are shown. H Schematic diagram of the timeline of cell-penetrating peptide (CPPtat, CPPtat-WT, or CPPtat-3A) treatment in the AKT/NRASV12 mouse model. The spontaneous HCC mouse model was established by hydrodynamic tail vein infection. Subsequently, 100 mg/kg of the polypeptides were injected intraperitoneally into mice every 5 days. The schematic was created with BioRender.com (License #RZ28F649PJ, ©2025). I Representative livers of AKT/NRASV12 mice treated with CPPtat, CPPtat-WT, or CPPtat-3A. J The ratio of liver to body weight was calculated (n = 10 mice per group). HCC tissues were harvested for RT-qPCR (K), immunoblotting and sWGA pull-down assays (L). For (J, K), data are presented as mean ± SD, *P < 0.05, ***P < 0.001. M Kaplan–Meier survival curves illustrating the overall survival (OS) of patients with HCC in the TCGA-LIHC cohort according to METTL3 and MCM10 levels, P < 0.05.