NCBP1 promotes the malignant progression of Wilms' tumor through stabilization of KPNA2 mRNA.

Nephroblastoma, also known as Wilms' tumor (WT), is the most common malignant renal tumor in children under 5 years of age. Despite a generally favorable prognosis, approximately 15% of cases experience recurrence. Currently, treatment options for refractory and recurrent WT remain limited, and targeted therapeutic strategies are still under investigation. NCBP1 is a core component of the cap-binding complex and plays a role in mRNA processing, transport, and translational regulation; however, its involvement in the initiation and progression of WT has not yet been elucidated. This study utilized bioinformatics analysis to identify that NCBP1 is highly expressed in WT tissues and is associated with a poor prognosis. Molecular experiments further confirmed that NCBP1 is significantly overexpressed in the WT cell lines 17.94 and HFWT. Functional assays demonstrated that silencing NCBP1 suppresses the proliferation, migration, invasion, and tumorigenic potential of both 17.94 and HFWT cells. Through screening for NCBP1-interacting proteins, KPNA2 was identified, and a positive correlation was observed between the expression levels of KPNA2 and NCBP1 in WT tissues. Through RNA immunoprecipitation experiments, we further validated the interaction between NCBP1 and KPNA2 in WT cells. Silencing of NCBP1 resulted in reduced stability and expression levels of KPNA2 mRNA in 17.94 and HFWT cells. Furthermore, KPNA2 overexpression not only enhanced the proliferation, migration, and invasion capabilities of 17.94 and HFWT cells, but also partially counteracted the inhibitory effects of NCBP1 silencing on these malignant cellular behaviors. In conclusion, the findings of this study elucidate the involvement of NCBP1 in the malignant progression of WT. NCBP1 enhances the stability of KPNA2 mRNA, thereby upregulating KPNA2 expression and subsequently promoting the malignant progression of WT cells.