USP25 Regulated Multiple Myeloma Cell Cycle Through STAT3 Ubiquitination

Abstract Background Constitutively activated STAT3 (Signal transducer and activator of transcription 3) has been seen in Multiple Myeloma (MM). However, STAT3 regulator in MM remains enigmatic. Methods Herein, we applied public dataset analysis and identified USP25 (Ubiquitin carboxyl-terminal hydrolase 25) was a potential regulator of STAT3. We further applied western blot and IP to confirm the relation between USP25 and STAT3. Furthermore, we used cell cycle assay to assess the effect USP25 on MM cell cycle.RestultsUSP25 highly expressed in MM CD138+ cells, and support MM cell proliferation. In protein level, USP25 take part in IL-6/USP25/STAT3 axis and could directly down-regulated STAT3 ubiquitination. Using truncated form of USP25, we also proved UCH (Ubiquitin carboxyl-terminal hydrolase) domain of USP25 is critical for USP25-STAT3 binding, UIM (Ubiquitin interacting motif) domain is required for STAT3 ubiquitination, we further proved cell cycle changed by USP25 required STAT3 and cyclinD1, suggesting USP25 inhibition is promising in STAT3, cyclinD1 abnormal MM patients.