Graphical abstract. A) In ACH-3P cells, let-7 miRNAs are low because of high LIN28A and LIN28B. Because of low levels of let-7 miRNAs, ARID3A, ARID3B, and KDM4C are higher. The ARID3B complex binds the promoter regions of HMGA1, c-MYC, VEGF-A, and WNT1 and turns on these genes by chromatin modification. B) In LIN28 DKOs, let-7 miRNAs are higher. Elevated let-7 miRNAs target HMGA1, c-MYC, VEGF-A, and WNT1, leading to reduced expression of these genes. In addition, the elevated let-7 miRNAs also target ARID3A, ARID3B, and KDM4C. This results in less binding of the ARID3B complex to promoter regions of HMGA1, c-MYC, VEGF-A, and WNT1, leading to reduced expression of these genes. C) In ARID3B KO cells, the ARID3B complex is disrupted. KDM4C cannot bind to DNA in the absence of ARID3B, which turns off this pathway of chromatin modification, and hence, HMGA1, c-MYC, VEGF-A, and WNT1 are reduced.