Ncoa7 Promotes Oral Cancer Progression Through Ros-Regulated Ferroptosis

Oral cancer is the most common invasive malignancy in head and neck regions with a worse prognosis. Recent studies revealed the role of nuclear receptor coactivator 7 (NCOA7) in promoting tumorigenesis. However, the molecular mechanism remains unclear. Human oral cancer tissues were collected and stained with HE and NCOA7. The expression of NCOA7 between normal and tumor tissues was compared, accompanied by the correlation comparison with clinicopathological parameters. In vivo, a 4-nitroquinoline 1-oxide (4-NQO) mouse model was established to investigate the correlation of NCOA7 with oral cancer development. In vitro, NCOA7 was knocked down using siRNA. The proliferation, migration, invasion, and ferroptosis were evaluated using CCK8, 2D and 3D spheroid migration and invasion assays, qRT-PCR, and immunocytochemistry. All clinical and animal protocols were approved by the Institutional Ethics Committee. Significantly high expression of NCOA7 was found in oral cancer tissues, and patients with higher NCOA7 levels demonstrated to have poor prognosis. In vivo, NCOA7 expression was significantly elevated with the dynamic advances in oral cancer, accompanied by the reduction of ferroptosis. In vitro, NCOA7 knockdown statistically reduced the proliferation, migration, and invasion of oral cancer cells, which can be rescued using antioxidants. Moreover, high levels of reactive oxygen species (ROS) and ferroptosis were evaluated in NCOA7 knockdown cells, while ROS inhibition could decrease ferroptosis, which can be further rescued using erastin, a ferroptosis inducer. NCOA7 promotes oral cancer progression by inhibiting ferroptosis through ROS signaling. NCOA7 might be a new therapeutic target for oral cancer.