Fig. 5

Demethylation at enhancer significantly negatively correlated with MCM2 mRNA expression. A Diagram showing the CpG islands in the promoter region of human MCM2 gene. B Heatmap showing overall methylation patterns in the DNA sequence of human MCM2 gene. C Correlation heatmap visualizing the relationship between MCM2 mRNA expression and the methylation level of CpG site at MCM2 promoter region. D–F Scatter plot showing that MCM2 mRNA expression significantly negatively correlated with the methylation level of MCM2 enhancer region (cg08889930) in HCC patients from 3 independent datasets. G MCM2 mRNA expression in Huh7 cells significantly increased after decitabine treatment **** p < 0.0001, based on ANOVA. H MCM2 mRNA expression in Huh7 cells significantly reduced after CPI-455 treatment. **** p < 0.0001, based on ANOVA. I–J Representative immunoblot of HCC cells (Huh7) lysates showing that decitabine increased MCM2 protein expression and CPI-455 attenuated MCM2 protein expression. TCGA, The Cancer Genome Atlas; ANOVA, analysis of variance; HCC, hepatocellular carcinoma