RNF220 promotes the proliferation of leukaemic cells and reduces the degradation of the Cyclin D1 protein through USP22

Ring finger proteins contain a characteristic ring finger motif and perform a wide range of biological functions in living organisms. These genes are abnormally expressed in many cancers. We found that the expression level of Ring finger protein 220 (RNF220) was negatively correlated with the disease-free survival (DFS) and overall survival (OS) of acute myeloid leukaemia (AML) patients. Moreover, the mRNA level of this gene is significantly higher in the bone marrow cells of AML patients than in the mobilized peripheral blood haematopoietic stem cells of healthy donors. The overexpression of RNF220 promotes the proliferation of AML cells and accelerates the transition from G1 phase to S phase. Increased protein levels and decreased ubiquitylation levels of Cyclin D1 were observed in the nuclei of cells overexpressing RNF220 compared to those of control cells. The protein level of USP22 was also increased in cells overexpressing RNF220. RNF220 cannot enhance the stability of the Cyclin D1 protein without increased expression of the USP22 protein. Our study provided proof of principle to show that RNF220 promotes stabilization of the Cyclin D1 protein via USP22.