USP9X promotes acute myeloid leukemia progression and adriamycin resistance by regulating METTL7A deubiquitination.

Adriamycin (ADR) resistance remains a significant obstacle in treating acute myeloid leukemia (AML), with most patients eventually developing resistance, resulting in poor prognosis. The deubiquitinase USP9X has been implicated in chemoresistance in AML, while its specific role in ADR resistance remains unclear. Our study proved that the expression levels of USP9X and METTL7A were significantly elevated in HL60/ADR cells. The deficiency of both USP9X and METTL7A obviously inhibited cell growth, as evidenced by decreased colony formation, cell migration, invasion, and proliferation, along with increased cell death. Furthermore, USP9X stabilizes METTL7A stability by regulating its deubiquitination. Notably, up-regulation of METTL7A successfully reversed the growth inhibition caused by USP9X knockdown. These findings were further validated in BALB/c nude mice, where the loss of USP9X and METTL7A reduced tumor growth, and promoted tumor cell apoptosis. Taken together, our findings revealed that USP9X promotes HL60/ADR cell growth in a METTL7A deubiquitination-dependent manner. Therefore, targeting USP9X or METTL7A could provide a promising therapeutic strategy to overcome ADR resistance in AML.