Fig. 1

Mettl16 is essential for de novo hepatocarcinogenesis, but dispensable for normal hepatogenesis. A Spatial feature plots of METTL16 expression in HCC patient. N, non-tumor region; T, tumor region. B Schematic of the design and representative genotyping results of the liver-specific Mettl16 conditional KO (cKO) mouse model. C Western blotting showing the Mettl16 KO efficiency of liver of Mettl16 wild-type (WT), heterozygous cKO (Mettl16^fl/+), and homozygous cKO (Mettl16^fl/fl) mice. D Western blotting showing the Mettl16 KO efficiency in the livers of 0- and 5-week-old homozygous cKO mice. E Kaplan–Meier survival curves of Mettl16 WT, heterozygous cKO and homozygous cKO mice. F, G Body (F) and liver (G) weight of adult Mettl16 WT, heterozygous cKO and homozygous cKO mice (n = 10 for WT; n = 6 for Mettl16^fl/+; n = 9 for Mettl16^fl/fl; mean ± SEM). H Representative liver images of adult Mettl16 WT, heterozygous cKO and homozygous cKO mice. I Representative H&E staining images of adult Mettl16 WT, heterozygous cKO and homozygous cKO mice. J Representative H&E staining images of liver sections from Mettl16 cKO mice at indicated time points postnatally. K, L Relative abundance of CD4⁺ T cells, CD8⁺ T cells, B cells, NK cells, and macrophages in Mettl16 heterozygous cKO (K) and homozygous cKO (L) mice as compared to Mettl16 WT (n = 3–5; mean ± SEM). M Western blotting showing the cleaved Caspase-3 level in the livers of Mettl16 WT, heterozygous cKO, and homozygous cKO mice. N Schematic of HDTVi-induced de novo hepatocarcinogenesis model. O Representative liver (upper panel) and H&E staining (lower panel) images of tumors generated in Mettl16 WT, heterozygous cKO, and homozygous cKO mice. P, Q The bar plots showing the ratio of liver weight to body weight (P) and the nodule numbers per liver (Q) (n = 6–8; mean ± SEM). R Representative images showing the tumor (T) and adjacent normal (N) tissue in the HDTVi-HCC model. S Western blotting showing the expression levels of Mettl16 in HCC tumors and adjacent normal liver tissues. Statistical analyses: un-paired t-test (F, G, K, L, P, Q). ns, not significantly; *P < 0.05; **P < 0.01