Fig 1: UHRF1 promotes HOXB13-mediated transcriptional regulation of LTK by downregulating SFMBT2. Schematic representation of the experimental findings showing that UHRF1 binds CpG islands in the SFMBT2 promoter, reducing its transcription. Lower SFMBT2 levels are associated with increased HOXB13 expression and enhanced binding of HOXB13 to the LTK promoter, leading to elevated LTK expression. A WB analysis of HOXB13 and LTK expression levels in HepG2 cells following UHRF1 overexpression. B WB analysis of HOXB13 and LTK expression levels in HepG2 cells following SFMBT2 overexpression. C WB analysis of UHRF1, SFMBT2, HOXB13, and LTK expression levels in HepG2 cells co-overexpressing UHRF1 and SFMBT2. D IHC analysis of HOXB13 expression in tumour tissues. HOXB13 expression was elevated in the UHRF1-overexpression group compared with the control group, while SFMBT2 co-overexpression reversed this upregulation. E IHC analysis of LTK expression in tumour tissues. LTK expression was increased in the UHRF1-overexpression group compared with the control group, while SFMBT2 co-overexpression reversed this phenotype. F ChIP assay evaluating LTK promoter enrichment in HepG2 cells. After UHRF1 overexpression, chromatin precipitated with HOXB13 antibody showed significantly increased binding of HOXB13 to the LTK promoter DNA. G WB confirming successful overexpression of HOXB13 in HepG2 cells after transfection with HOXB13-expressing plasmids. H Dual-luciferase reporter assay in HepG2 cells co-transfected with wild-type or mutant LTK promoter constructs (mutating the highest-scoring HOXB13 binding site predicted by the JASPAR database) and HOXB13-expressing plasmids. I: Dual-luciferase reporter assay in HepG2 cells co-transfected with wild-type or mutant LTK promoter constructs and SFMBT2-expressing plasmids.