USP7-mediated NUF2 deubiquitination accelerates ovarian cancer progression through regulating SLC7A11 expression
Ovarian cancer is highly lethal malignancy. Previous studies have indicated that Ndc80 kinetochore complex component (NUF2) exhibited oncogenic properties in ovarian cancer. This study aimed to investigate the underlying mechanisms by which NUF2 contributes to ovarian cancer progression. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was conducted to measure the mRNA expression levels of NUF2 and solute carrier family 7 member 11 (SLC7A11). The protein expression of NUF2, ubiquitin-specific protease 7 (USP7) and SLC7A11 was examined through Western blot. Cell proliferation was determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2 H-tetrazolium bromide (MTT) and 5-ethynyl-2'-deoxyuridine (EdU) assays. Cell apoptosis and invasion were detected by flow cytometry and transwell invasion assay, respectively. Ferroptosis was assessed through detecting ferrous ion (Fe NUF2 was significantly elevated in ovarian cancer cells. Knockdown of NUF2 markedly inhibited ovarian cancer cell proliferation and invasion while promoting apoptosis and ferroptosis. Mechanistically, USP7 stabilized NUF2 by mediating its deubiquitination. USP7 depletion inhibited cell proliferation and invasion, and promoted cell apoptosis and ferroptosis in ovarian cancer cells, effects that were mediated through NUF2 downregulation. Furthermore, SLC7A11 was overexpressed in ovarian cancer, and NUF2 positively regulated its expression. NUF2 depletion decreased SLC7A11 expression, thereby suppressing ovarian cancer progression. Additionally, SLC7A11 overexpression could reverse the inhibitory effects of USP7 knockdown on ovarian cancer progression. USP7 stabilized NUF2 expression via deubiquitination to accelerate ovarian cancer progression through regulating SLC7A11 expression.