A. MUC1-C activates (i) BMI1 and RING2 by MYC-mediated mechanisms, and (ii) RING1 through the NF-κB p65 pathway 36. Thus, targeting MUC1-C is associated with downregulation of BMI1, RING2 and RING1 expression in TNBC and NSCLC cells 36. B. Schemas of the BMI1, RING2 and RING1 promoters with highlighting of the MYC and NF-κB binding sites. C. MUC1-C binds directly to BMI1 by an interaction dependent of the MUC1-C CQC motif 36. Complexes of MUC1-C and BMI1 have been detected on the CDKN2A promoter 36. In support of the depiction, targeting MUC1-C genetically or with the GO-203 inhibitor (i) decreases H2A ubiquitylation, (ii) increases HOXC5 and HOXC13 expression, and (iii) activates CDKN2A and expression of p16INK4a 36. The findings thus support a role for MUC1-C in contributing to BMI1-driven tumor promotion, self-renewal capacity, the CSC state, and genomic instability.