NCOA7 promotes OSCC progression by inhibiting ROS-regulated ferroptosis.

BACKGROUND

Oral squamous cell carcinoma (OSCC) is the commonest invasive malignancy in the 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.

METHODS

Human OSCC tissues were collected and stained with H&E and NCOA7. The expression of NCOA7 in both normal and tumor tissues was compared, along with a correlation analysis with clinicopathological parameters. In vitro, NCOA7 was knocked down, and the proliferation, migration, invasion, and ferroptosis were evaluated using CCK-8, transwell and 3D spheroid migration and invasion assays, qRT-PCR, western blot, and immunocytochemistry. The effects of NCOA7 on intracellular reactive oxygen species (ROS) and ferroptosis in OSCC cells were investigated under the treatment of antioxidants N-Acetyl-L-cysteine (NAC), ferroptosis inhibitors deferoxamine mesylate (DFO) and ferrostatin-1 (Fer-1), and ferroptosis inducers erastin. The Institutional Ethics Committee approved all clinical protocols.

RESULTS

Significantly high expression of NCOA7 was found in OSCC tissues and was linked to the advancement of OSCC. In vitro, NCOA7 knockdown statistically reduced the proliferation, migration, and invasion of OSCC cells, which could be rescued using NAC or Fer-1. Moreover, NCOA7 knockdown cells exhibited significantly high levels of ROS and ferroptosis, which could be reversed using NAC or DFO or Fer-1. Further investigations revealed that inhibiting ROS in OSCC cells reduced ferroptosis, while erastin could reverse its inhibitory effect.

CONCLUSIONS

NCOA7 promotes OSCC progression by inhibiting ferroptosis through ROS signaling. NCOA7 might be a new therapeutic target for OSCC.