OTUB1 promotes the progression of acute myeloid leukemia by regulating glycolysis via deubiquitinating c-Myc

Acute myeloid leukemia (AML) is the most common type of adult leukemia and patients with AML often have poor prognosis, for which there remains an urgent need to identify novel selective targeted therapy. OTUB1, a deubiquitinating enzyme, is associated with the malignant progression of multiple cancers. However, the role of OTUB1 in AML is still unclear and warrants further investigations. Our study revealed that the expression of OTUB1 is significantly upregulated in AML. Next, we observed that knockdown of OTUB1 inhibits AML cell proliferation and promotes AML cell apoptosis and G0/G1 phase blockade using CCK-8 assay, western blotting, and flow cytometry. Mechanistically, OTUB1 drives the malignant development of AML through regulating cellular aerobic glycolysis by deubiquitinating c-Myc. Lastly, by investigating whether inhibition of OTUB1 enhances the sensitivity of chemotherapeutic agents commonly used in the clinical treatment of AML, we found that combining OTUB1 inhibition with daunorubicin treatment could achieve better therapeutic effects in AML. In brief, our results revealed a novel mechanism by which OTUB1 promotes glycolysis via deubiquitinating c-Myc in AML. Consequently, targeting OTUB1 may provide a promising strategy for enhancing the efficacy of AML treatment.