PSMC2 drives tumor progression in nasopharyngeal carcinoma by inhibiting ferroptosis through STAT3.

Nasopharyngeal carcinoma (NPC) mortality is driven primarily by malignant proliferation and metastasis. Although PSMC2 contributes to tumor progression, its mechanistic role in NPC pathogenesis remains undefined. Protein expression levels were detected via WB and immunohistochemistry. Cell activity was measured by a CCK8 assay. The cell migration ability was detected via wound-healing assays. Cell death was detected by flow cytometry. The levels of ROS, lipid peroxidation and iron ions were observed via confocal microscopy. The level of GSH was detected with a microplate reader. The growth abilities of the tumors were analyzed with a subcutaneous tumor model. PSMC2 is highly expressed in NPC. Compared with those in the control group, cell proliferation activity and migration ability were decreased, the phosphorylation level of STAT3 was decreased, the protein expression of CPT1 and GPX4 was downregulated, ROS and lipid peroxidation levels were increased, GSH levels were significantly decreased, iron ion levels were significantly increased, and ferroptosis levels were increased in the PSMC2 knockdown group. Compared with those in the PSMC2-knockdown group, the cell proliferation activity and migration ability were increased, the phosphorylation level of STAT3 was increased, the protein expression of CPT1 and GPX4 was increased, the ROS and lipid peroxidation levels were decreased, the GSH levels were significantly increased, the iron ion levels were significantly decreased, and the cell activity was increased. Tumor growth was significantly reduced with PSMC2 knockdown. PSMC2 upregulates CPT1 and GPX4 by activating STAT3, inhibits ferroptosis induced by lipid peroxidation, and drives malignant proliferation and metastasis in NPC.