CDC25A inhibition sensitizes melanoma cells to doxorubicin and NK cell therapy.

Cell division cycle 25 (CDC25) phosphatases serve as crucial regulators of cell cycle phase transitions and essential components of the checkpoint machinery involved in DNA damage response. Emerging evidence indicates the oncogenic potential of CDC25 family members across various cancers. However, comprehensive insights into the expression pattern and function of the CDC25 family in diverse cancers remain unexplored. In our study, we investigated CDC25 family using multiple databases, including gene expression levels, molecular signatures, diagnosis value, and prognostic value in pan-cancer. Furthermore, we focused on melanoma and systematically explored CDC25A expression and its clinical correlations. As a result, the expression of CDC25 family members is significantly abnormal in most cancers, correlating with poorer prognosis. CDC25 family members are differently regulated by DNA methylation and genetic alterations across various cancers. In addition, CDC25 family plays a critical role in the malignant progression of melanoma. Functional investigation reveals that CDC25A inhibition suppresses the proliferation of melanoma cells and sensitizes melanoma cells to chemotherapy and NK cell therapy. In conclusion, our study suggests that CDC25 family may serve as a significant biomarker for diagnosis and prognosis across multiple cancers, with CDC25A as a promising therapeutic target for melanoma.