Fig. 5
From: MicroRNA regulation of cancer stem cells in the pathogenesis of breast cancer
miRNA-mediated regulation of the BCSCs via targeting the BMI-1 signaling pathway. a To support self-renewal of stem cells by BMI-1 (a component of PRC1), PRC1 suppresses the expression of the Ink4a locus that encodes the p16Ink4a and the p19Arf genes by trimethylation of H3-K27 (H3K27me3) and ubiquitination of H2A-K119 (H2AK119Ub). The chromodomain of CBX binds to H3K27me3 and RING1 deposits monoubiquitin on H2AK119. b p16Ink4a inhibits the phosphorylation of RB by the cyclin D/Cdk4/6 complex and E2F-dependent transcription of RB that finally inhibit cell cycle progression. p19Arf causes high levels of p53 via preventing MDM2-mediated p53 degradation, which represses cell cycle progression and promotes apoptosis. The immediate targets of miRNAs are marked