Targeting KIF23 inhibits cell proliferation and primary chemoresistance in cervical cancer by inactivating the MYH9/MCM2/PCNA pathway

作者：Ying Zhu, Qian Wang, Yuan Zhang, Yahui Liu, Haini Fu, Zike Yang, Xiaojie Deng, Suiqun Guo · 发表于：Clinical and Translational Medicine · 年份：2026 · DOI：10.1002/ctm2.70652 · 被引用次数：2 · 研究领域：Ubiquitin and proteasome pathways、DNA Repair Mechanisms、Microtubule and mitosis dynamics

BACKGROUND: Kinesin family member 23 (KIF23) is recognised as an important tumour promoter involved in the pathogenesis of various cancers. However, its role and underlying molecular mechanisms in regulating cervical cancer (CC) growth and primary chemoresistance remain to be fully elucidated. METHODS: The expression and prognostic significance of KIF23 were initially assessed through bioinformatic analyses and subsequently validated in clinical specimens. To evaluate the effects of KIF23 on cell proliferation and cisplatin (DDP) sensitivity in CC cells, in vitro and in vivo experiments were conducted using CRISPR/Cas9 knockout, overexpression and mouse xenograft models. Co-immunoprecipitation, protein half-life assays and ubiquitination assays were employed to elucidate the interactions and regulatory mechanisms involving KIF23, myosin heavy chain 9 (MYH9), minichromosome maintenance protein 2 (MCM2) and proliferating cell nuclear antigen (PCNA), thereby revealing the molecular basis of KIF23-mediated CC progression and primary chemoresistance. RESULTS: KIF23 is highly expressed in CC tissues and is significantly correlated with poor prognosis and DDP resistance in patients. The knockout of KIF23 inhibited cell proliferation, induced G1-phase arrest and enhanced chemosensitivity to DDP. Mechanistically, the C-terminal domain of KIF23 was found to directly bind to the myosin tail domain of MYH9. This interaction stabilises MYH9 by recruiting deubiquitinase 7 (ubiquitin-specif...