KIF4A promotes genomic stability and progression of endometrial cancer through regulation of TPX2 protein degradation

Abstract Background Kinesin family member 4A (KIF4A) belongs to the kinesin superfamily proteins, which are closely associated with mitophagy. However, the role of KIF4A in endometrial cancer (EC) remains poorly characterized. Here, we aimed to explore the function and regulatory mechanisms of KIF4A in EC. Methods The expression of KIF4A was evaluated by quantitative polymerase chain reaction, western blotting, and immunohistochemistry. Cell proliferation was measured using Cell Counting Kit-8, clone formation, and 5-ethynyl-2′-deoxyuridine staining assays. Flow cytometry was performed using annexin V/propidium iodide (PI) to identify apoptotic cells and PI staining to analyze the cell cycle. RNA-seq, coimmunoprecipitation, immunofluorescence, and western blotting were performed to explore the underlying mechanism. Results In this study, we demonstrated that KIF4A was upregulated and predicted a poor prognosis in patients with EC. KIF4A knockdown in EC cells resulted in attenuated proliferative capacity and promoted cell cycle arrest and apoptosis induced by increased DNA damage. Mechanistic investigations indicated that KIF4A knockdown exacerbated DNA damage repair and response by regulating the stability of the spindle assembly factor TPX2. Conclusions KIF4A promotes genomic stability and progression of endometrial cancer through regulation of TPX2 protein degradation. KIF4A may serve as a promising therapeutic target for endometrial cancer