Figure 9.

The Schematic Illustrates a Model of the Differentiation of Human Mesenchymal Stem Cells into Cancer Cells via miR675

Oncogenic miR675 promotes the interaction between CREB and P300, which leads to the high expression of P62. That P62 competes with STED2 to bind histone H3 greatly reduces the STED2-binding capacity with substrate histone H3, triggering a reduction of three methylations on histone H3 36th lysine (H3K36me3); thereby, the H3K36me3-hMSH6-SKP2 tri-complex is decreased. Meanwhile, the ternary complex occupancy capacity on chromosome is absolutely reduced, preventing normal DNA repair. By virtue of the reductive degradation ability of SKP2 for aging histone H3.3 bound to damaged DNA, the aging histone H3.3 repair is delayed and eliminated. That the damaged DNA escaped repair can lead to the abnormal expression of some cell cycle- and metabolism-related genes, causing the human mesenchymal stem cell malignant transformation.