Figure 5.

Schematic illustration of a mechanism by which DNA methylation of the Nanog promoter modulated the switch of non‐CSCs into CSCs under the control of the miRNA‐135 level. The miR‐135a level, once elevated, lowered the methylation level of the CG5 site in the Nanog promoter by directly targeting DNMT1. SMYD4 bound to the unmethylated Nanog promoter to activate Nanog expression in Nanog‐negative tumor cells. miR‐135a expression was upregulated by elevated FOXM1, the latter was activated by TNF‐α administration. The TNFα/FOXM1/miR‐135a/DNMT1 pathway was involved in the conversion of non‐CSCs into CSCs.