Inducing the degradation of KRAS represents a novel strategy to combat cancers with KRAS mutation. In this study, we identify ubiquitin-specific protease 2 (USP2) as a novel deubiquitinating enzyme of KRAS in multiple myeloma (MM). Specifically, we demonstrate that gambogic acid (GA) forms a covalent bond with the cysteine 284 residue of USP2 through an allosteric pocket, inhibiting its deubiquitinating activity. Inactivation or knockdown of USP2 leads to the degradation of KRAS, resulting in the suppression of MM cell proliferation in vitro and in vivo. Conversely, overexpressing USP2 stabilizes KRAS and partially abrogates GA-induced apoptosis in MM cells. Furthermore, elevated USP2 levels may be associated with poorer prognoses in MM patients. These findings highlight the potential of the USP2/KRAS axis as a therapeutic target in MM, suggesting that strategically inducing KRAS degradation via USP2 inhibition could be a promising approach for treating cancers with KRAS mutations.

Objective To expand the application of EOS in orthopedic diagnosis and treatment by comparing EOS and CT in the measurement of tibial tubercle-trochlear groove(TT-TG)distance of patellar dislocation.Methods The clinical and complete imaging data(EOS and CT)of 35 cases of patellar dislocation(dislocation group)and 35 cases of non-patellar dislocation(non-dislocation group)were analyzed retrospectively.Results The age difference between the dislocation group and the non-dislocation group was statistically significant(P＜0.05).The TT-TG distance was measured by EOS in the dislocation group(20.19±1.05)mm and the non-dislocation group(13.33±1.17)mm,and the difference between the two groups was statistically significant(P＜0.05).The TT-TG distance was measured by CT in the dislocation group(21.51±1.11)mm and the non-dislocation group(14.21±1.11)mm,and the difference between the two groups was statistically significant(P＜0.05).Bland-Altman plot showed that only three cases were outside the 95％confidence interval.Conclusion Accurate TT-TG distance can be obtained by using EOS system in imaging evaluation of patients with patellar dislocation,which provides a new measurement method for diagnosis and treatment evaluation of patellar dislocation.