KIF15 promotes clear cell renal cell carcinoma growth by downregulating p53 pathway through USP15-mediated MDM2 deubiquitylation

Clear cell renal cell carcinoma (ccRCC) is the most common malignant cancer in kidney. Exploring new therapeutic targets is crucial to improving the ccRCC patients’ overall survival. Kinesin family member 15 (KIF15), a member of the kinesin superfamily proteins, participates in various biological processes. However, the role and action mechanisms of KIF15 in ccRCC remain unknown. We observed that KIF15 was highly expressed in ccRCC tissues and its expression was negatively correlated with the prognosis of ccRCC patients. In vitro experiments showed that KIF15 promoted the proliferation of ccRCC cells. Consistently, in vivo assays showed that KIF15 accelerated tumor growth in ccRCC-bearing nude mice. Further investigation revealed that zinc finger protein 750 (ZNF750) repressed the transcription of KIF15 by directly binding its promoter region, simultaneously repressing ccRCC cell growth. Mechanistically, KIF15 stabilized MDM2 via enhancing USP15-mediated deubiquitylation, thus suppressing the p53 pathway. Our study indicates the oncogenic role and molecular mechanisms of KIF15 in ccRCC progression and provides valuable insights into potential therapeutic strategies for ccRCC.