Abstract

Cervical cancer is one of the major threats to women’s health worldwide. Nuclear Cap Binding Protein 2(NCBP2) plays a significant role in various cancers, and mitophagy, as a cellular homeostasis regulation mechanism, is closely related to tumorigenesis and development. However, the specific mechanisms by which NCBP2 regulates mitophagy in cervical cancer remain unclear. Bioinformatics was used to screen cervical cancer-related genes and mechanisms. The effects of NCBP2 on the viability, migration, and mitochondrial function of cervical cancer cells were investigated using CCK-8, EdU, and Transwell assays. Comprehensive experimental methods, including RT-qPCR and Western blot, were employed to elucidate the potential mechanisms of NCBP2. NCBP2 was found to be significantly upregulated in cervical cancer and promoted the in vitro proliferation, migration, and invasion of cervical cancer cells. Mechanistically, NCBP2 regulated the alternative splicing of KIF23 to facilitate cervical cancer progression. NCBP2 also regulated mitophagy in cervical cancer cells via the KIF23-PGAM5 axis. Moreover, FBXW8 inhibited the overactivation of mitophagy and exerted tumor-suppressive effects by ubiquitinating and degrading NCBP2. This study reveals that NCBP2 regulates alternative splicing and mitophagy to influence cervical cancer progression, providing new potential therapeutic targets and strategies for cervical cancer treatment. Graphical In normal cervical tissues, FBXW8 maintains normal mitophagy and inhibits tumorigenesis by ubiquitinating and degrading NCBP2. However, in cervical cancer tissues, the upregulation of NCBP2 suppresses the alternative splicing of KIF23 and overactivates mitophagy by promoting the expression of PGAM5, thereby facilitating the progression of cervical cancer