Deubiquitinase USP38 Stabilizes PLK1 Expression to Boost DNA Damage Repair in Ovarian Cancer

Ovarian Cancer (OC) is one of the most prevalent and severe gynecological malignant tumors. DNA damage repair (DDR) is essential in maintaining genome stability. This study aims to investigate the effects and mechanisms of USP38 and PLK1 on DNA damage repair and malignant behavior in OC cells. Bioinformatics analysis was conducted to assess the expression of USP38 and PLK1 in OC tissues and predict downstream target proteins of USP38 and potential deubiquitination sites of target proteins. Expression levels of USP38 and PLK1 were analyzed by qPCR and WB. Cell proliferation ability was assessed by EdU experiment assay and colony formation assay. Apoptosis level was analyzed by TUNEL assay. The CO-IP assay was applied to assess the binding of USP38 and PLK1. The ubiquitination experiment was employed to evaluate the ubiquitination of PLK1 by USP38. The comet assay was utilized to analyze DNA damage in cells. USP38 and PLK1 were highly expressed in OC. The binding of USP38 to PLK1 mediated the deubiquitination of PLK1 and stabilized the protein level of PLK1. Silencing USP38 reduced the proliferation ability of OC cells and elevated the Apoptosis rate of Cancer cells. Mechanically, silencing USP38 decreased the expression level of PLK1 protein, repressing DDR in Cancer cells. Deubiquitinase USP38 binds to PLK1 to stabilize PLK1 expression, facilitating DDR in OC cells and enhancing Cancer cell proliferation, thereby reducing the Apoptosis rate of Cancer cells.