Fig. 7: Schematic diagram of KDM5B-mediated regulation for Ewing sarcoma proliferation by the FBXW7/CCNE1 axis.

(Left) In Ewing sarcoma cells, KDM5B overexpression inhibits FBXW7 transcription by demethylation of H3K4me3 at the promoter region, blocking the degradation of CCNE1 and accumulating CCNE1 protein, leading to acceleration of cell cycle process and cell proliferation of Ewing sarcoma. (Right) Epigenetic drug AS-8351 suppresses the function of KDM5B and elevates H3K4me3 level at the promoter region of FBXW7 gene, then up-regulates FBXW7 and enhances CCNE1 degradation, resulting in cell cycle arrest and tumor growth inhibition.