Regulation of Drp1 and enhancement of mitochondrial fission by the deubiquitinating enzyme PSMD14 facilitates the proliferation of bladder cancer cells

The protein Dynein-related protein 1 (Drp1) plays a crucial role in regulating the process of mitochondrial fission, which is known to be associated with the onset and progression of various human diseases. However, the specific impact of Drp1 on bladder cancer has yet to be fully understood. In previous studies, evidence to support the theory that the deubiquitinating enzyme proteasome non-ATPase regulatory subunit 14 (PSMD14) is responsible for stabilizing and promoting the activity of Drp1, ultimately resulting in increased mitochondrial fission, has been presented. The levels of PSMD14 in both bladder cancer tissues and cells were elevated, as confirmed through immunohistochemical and immunofluorescent staining. Co-immunoprecipitation and reciprocal co-IP tests demonstrated that PSMD14 and Drp1 interacted with each other. Upon knockdown of PSMD14, there was a corresponding decrease in Drp1 expression and subsequent inhibition of mitochondrial fission. However, when the Drp1 agonist Mdivi-1 was applied to cells where PSMD14 expression had been knocked down, a significant increase in cell growth was observed, partially restoring the cancer-promoting effects of PSMD14 on cell proliferation. In conclusion, these findings suggest that PSMD14 may stimulate bladder cancer cell proliferation by promoting mitochondrial fission through the stabilization of Drp1.