Fig. 4: UHRF1 loss leads to re-expression of tumor suppressor genes.
From: UHRF1 is a mediator of KRAS driven oncogenesis in lung adenocarcinoma
a Hierarchical clustering of differentially methylated regions in two KRAS mutant NSCLC cell lines (H358, A549) transfected with siRNAs against UHRF1, KRAS, or a negative control siRNA (siNeg). b Gene set enrichment analysis (GSEA) using GO terms, KEGG and Reactome gene sets on CpGs differentially methylated between cells treated with siUHRF1 compared to control cells. Plots show the top aggregated pathways enriched in hypomethylated genes (“down”) ranked by gene ratio (gene/total gene) for a given pathway. c Hierarchical clustering of differential gene expression in two KRAS mutant NSCLC cell lines (H358, A549) transfected with siRNAs against UHRF1, KRAS, or siNeg. d Volcano plot of differential gene expression between siUHRF1 and siNeg in two KRAS mutant NSCLC cell lines (H358, A549). Green points – examples of significantly overexpressed tumor suppressor genes (TSGs), blue point – UHRF1 and KRAS. e Venn diagrams of significantly (FDR < 0.05) downregulated (left) or upregulated (right) genes in cell treated with siUHRF1 or siKRAS. Both up- and downregulated genes show significant overlap (p < 0.00001, hypergeometric test) between siUHRF1 and siKRAS. f Venn diagram of tumor suppressor genes (TSGs) hypomethylated with siUHRF1 (EPIC methylation array dataset) and TSGs upregulated with siUHRF1 (RNAseq dataset) in A549 and H358 cells.
