Fig. 2

Epigenetic modifications of colorectal CSCs. A DNA methylation. DNA methyltransferase 1 (DNMT1) participates in the activation of the Wnt/β-catenin pathway to maintain the stemness of CRC cells. After knocking down DNMT1 or treating cells with the DMNT1 inhibitor 5-aza-2'-deoxycytidine (5-AzaDC), the transcriptional activity of β-catenin in the nucleus was significantly reduced. B Histone methylation. Repressive H3K9me2 mark wasmarks are removed by histone demethylases (KDM3A/B), which simultaneously recruit lysine methyltransferase (MLL1), which mediates for the H3K4me3 modification to and thus promotes the expression of the Wnt target genes AXIN2 and DKK1. C Histone acetylation. The Wnt/β-catenin target gene PROX1 interacts with the Notch1 promoter and recruits the nucleosome remodeling and deacetylase (NuRD) complex, which deacetylates histones and remodels chromatin to block Notch1 transcription. D Noncoding RNAs. cis-HOX (a cyclic RNA) can binds to HOXC10 mRNA in the cytoplasm to inhibit the KSRP-dependent degradation of HOXC10 mRNA. The increased HOXC10, the level of which has been increased, enters the nucleus and drives FZD3 expression to activate the Wnt/β-catenin signaling pathway