Ubiquitin E3 ligase MYCBP2 targets KIF14 and contributes to acute myeloid leukemia progression.

Acute myeloid leukemia (AML) is a challenging hematological malignancy characterized by poor clinical outcomes. This study investigates the role of MYCBP2 in AML progression, focusing on its interaction with KIF14 and its involvement in ubiquitin-mediated processes. We found that MYCBP2 is overexpressed in AML samples compared to normal tissues, with high expression correlating with adverse clinical outcomes. Knockdown of MYCBP2 using siRNA significantly inhibited cell proliferation and promoted apoptosis in MOLM-13 and HL-60 AML cell lines. Flow cytometry revealed that MYCBP2 knockdown leads to cell cycle arrest in the G0/G1 phase. Gene Set Enrichment Analysis indicated that MYCBP2 is associated with the Ubiquitin-Mediated Proteolysis pathway, regulating KIF14 protein stability through ubiquitination. High KIF14 expression was linked to better overall survival, and KIF14 knockdown partially reversed the effects of MYCBP2 knockdown on cell viability and apoptosis. In vivo studies demonstrated that MYCBP2 knockdown significantly reduced tumor growth and enhanced apoptosis in a xenograft model. These findings support that MYCBP2 promotes AML progression at least in part by negatively regulating KIF14 stability, highlighting MYCBP2 as a potential therapeutic target. Future research should explore targeted therapies aimed at MYCBP2 and its downstream pathways to improve treatment strategies for AML.